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List six important ways that viruses impact domestic animals, humans, and science.
- Cause significant diseases in animals 2. Cause agriculturally and economically important exotic diseases 3. Cause important zoonotic diseases 4. Induce cancers in animals 5. Responsible for newly recognized diseases 6. Useful as vectors.
Which of the following are general aspects of viral biology that make viruses formidable? (Select all that apply)
What is one way to mitigate transmission of virus from a primary infected host?
Isolation of infected host.
Define 'serotype.'
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What occurs during the 'eclipse stage' of viral replication?
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Identify five ways or conditions that inactivate enveloped viruses.
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Which step of viral replication involves binding of the virus to the host cell?
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What is the primary determinant of host cell specificity related to viral infection?
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Describe how changing receptor usage can impact viral host range.
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What happens during the biosynthesis step of viral replication?
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What are virus proteins or gene products?
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What is a DIVA vaccine?
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Why should live virus and inactivated vaccines generally not be mixed?
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What is an advantage of replicating vaccines?
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What is a disadvantage of non-replicating vaccines?
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Drugs must be both ______ and effective.
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What is one barrier to producing effective antiviral drugs?
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What is the mode of action for antiviral drugs that target uncoating?
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What type of antiviral drug is Acyclovir?
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What does Tamiflu inhibit?
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What is the purpose of the 3CL protease in viral replication?
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What is the incubation period for systemic viral infections?
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Which of the following factors determine whether a virus remains localized or spreads systemically? (Select all that apply)
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Primary viremia is often subclinical or undetectable.
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What contributes to the febrile response during a viral infection?
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Secondary viremia usually occurs after approximately ______ days post-infection.
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List the three main host defense systems against viral infections.
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What is the main role of type I interferons in antiviral immunity?
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Match the following viral infections with their examples:
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What is the purpose of attenuated vaccines?
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Macrophage susceptibility plays an important role in the outcome of viral infection as they can either ingest and kill the virus or become ______.
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What must replication of all viruses result in?
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Why are RNA viruses more prone to developing genomic mutations?
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What is viral latency?
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What does CPE stand for?
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What is an example of a mechanism through which DNA viruses promote tumor development?
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Susceptible cells are those that can produce and release infectious virus.
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List three features of retroviral replication/biology that lend to their ability to cause neoplasia.
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The majority of infections in a population do not result in disease, referred to as the ______.
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Viral encoded proteins important in viral replication are excellent targets for developing antiviral therapeutics.
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What is a major anatomical portal viruses use to enter a host?
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Match the following terms with their definitions:
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What are virus proteins or gene products?
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Define a DIVA vaccine.
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Why should live virus and inactivated vaccines generally not be mixed?
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What are the advantages of replicating vaccines over non-replicating vaccines?
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What are some barriers to producing effective antiviral drugs?
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Which of the following is a mode of action for direct-acting antiviral drugs?
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What is the role of Tamiflu?
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What does Acyclovir target in viral replication?
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Match the antiviral drug with its action:
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List six important ways that viruses impact domestic animals, humans, and science.
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Which of the following aspects of viral biology contribute to their formidable nature? (Select all that apply)
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What are the five major primary sources of viruses that affect animals?
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Describe how viruses differ from bacteria in their multiplication.
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What is a serotype?
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What are the key steps of viral replication? (Select all that apply)
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What occurs during the 'eclipse stage' of viral replication?
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What is the primary determinant of host cell specificity for viruses?
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Which of the following can inactivate enveloped viruses? (Select all that apply)
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Explain how viral fusion proteins affect tissue tropism.
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What is the main difference between localized and systemic viral infections?
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Secondary viremia is often clinically detectable and occurs after approximately 8-9 days post-infection.
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List the four key factors that govern whether a virus remains localized or spreads systemically.
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Explain why macrophage susceptibility plays an important role in viral infection outcomes.
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In cases where viruses are released from the apical surface of cells, the infection is likely to be a ______ infection.
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What effect does hypothermia have on the anatomic site of viral replication?
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Which of the following is considered a first line of defense against viral infections?
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What roles do type I interferons play in antiviral immunity?
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Antibodies can neutralize viruses without involving cellular immunity.
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Match the type of antibody-mediated defense mechanism with its description:
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List one strategy that viruses use to evade the immune response.
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The main goals of vaccination are to prevent or reduce ______ and reduce transmission.
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What is the main reason why replication of all viruses must result in the production of positive (+) sense mRNA?
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Name two strategies that RNA viruses use to produce positive sense mRNA.
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Why are RNA viruses more prone to developing genomic mutations?
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What is advantageous about having a segmented genome?
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Which of the following viral proteins are excellent targets for developing antiviral therapeutics?
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What is the definition of cytopathic effects (CPE)?
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How does viral latency influence the choice of diagnostic test?
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What are the major anatomic portals that viruses use to enter and exit a host?
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List three factors that determine the outcome of viral infection.
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What mechanism describes a virus that induces ineffective antibodies?
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Describe how the skin and brain support viral persistence differently.
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Define transient and persistent viral infections.
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Which of the following mechanisms can viruses use to evade the adaptive immune response?
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List six important ways that viruses impact domestic animals, humans, and science.
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A protective protein shell in which the viral nucleic acid is packaged is called a __________.
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Identify how viruses differ from bacteria in their multiplication and energy production.
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What are the common nucleic acid types of viral genomes?
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All viruses are enveloped.
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Define 'serotype'.
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What is the function of capsid proteins in viruses?
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Which of the following factors can inactivate enveloped viruses?
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What is the primary determinant of host cell specificity for viruses?
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Explain one potential consequence of a virus altering its receptor usage.
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What is the main difference between localized and systemic viral infections?
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What are the incubation period characteristics of localized viral infections?
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List two key factors that govern whether a virus remains localized or spreads systemically.
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Why is secondary viremia more diagnostically useful?
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What are the three main host defense systems against viral infections?
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What role do type I interferons play in antiviral immunity?
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The innate immune response kicks in after days of viral replication.
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What is the primary function of neutralizing antibodies?
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What is the main goal of vaccination?
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What are two major contributing factors to the termination of an active viral infection?
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How do cytotoxic T cells help clear viral infections?
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The immune response to viral infections can sometimes contribute to the pathogenesis of __________ diseases.
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What are virus proteins or gene products?
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Define a DIVA vaccine.
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What is the main reason why live virus and inactivated vaccines should not be mixed?
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What are the advantages of replicating vaccines?
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What are the disadvantages of non-replicating vaccines?
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What are some barriers to producing effective antiviral drugs for veterinary use?
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What are the general modes of action for antiviral drugs targeting the virus life cycle?
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What is the function of Tamiflu?
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What does Paxlovid target?
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What stimulates the activation of fusion peptides in envelope glycoproteins?
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What is the difference between low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI)?
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Why must all viruses produce positive (+) sense mRNA?
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Which strategies do RNA viruses employ to produce positive sense mRNA?
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What is a major reason why RNA viruses are more prone to developing genomic mutations?
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What are two advantages of a virus having a segmented genome?
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What is the term for the process by which a virus introduces its genome into a cell?
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Define cytopathic effect (CPE).
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What are the major differences between transient and persistent infections?
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What are five mechanisms that viruses use to persist in an infected host?
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Define viral latency.
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Match the following mechanisms of viral tumor development with their descriptions.
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The majority of infections in a population result in disease.
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What principal factors determine the outcome of viral infection?
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Study Notes
Introduction to Viruses
- Six key impacts of viruses include causing significant animal diseases, economically important exotic diseases, zoonotic diseases, inducing cancers, triggering newly recognized diseases, and serving as vectors in biological studies.
- Viral transmission is efficient, characterized by high titers, environmental stability, and various transmission routes.
- RNA viruses exhibit high mutation rates, potentially causing significant disease or enabling cross-species infections.
- Viruses evade host defenses through mechanisms such as latency and antigenic variation, leading to persistence and potential for new infections.
- Unlike bacteria, viruses are not affected by common antibiotics and antiviral drugs are limited in availability.
Sources of Viral Infections
- Primary infection can spread through reinfection, mitigated by isolating infected hosts.
- Zoonotic transmission is reduced by minimizing interspecies interactions.
- Environmental infection severity can be lessened through sanitation and decontamination practices.
- Persistently infected hosts may require antiviral treatment or supportive care.
- Vector-borne transmission can be alleviated by implementing preventative measures.
Virus Structure and Classification
- Viral genomes can be RNA or DNA, with variations such as linear or circular, single-stranded or double-stranded, and can vary in size from 2kb to over 200kb.
- Capsids are protective protein shells, while envelopes are lipid membranes derived from host cells containing viral glycoproteins.
- Enveloped viruses are sensitive to heat, oxidation, freezing/thawing, desiccation, and detergents, making them easier to control through sanitation.
- Capsid proteins serve as optimal targets for serological testing and vaccine development due to their conservation across virus variants.
Viral Replication
-
Six key steps of viral replication:
- Attachment: Virion binds to host cell using viral attachment proteins and host receptors.
- Penetration: Virus crosses the host cell membrane via direct penetration or membrane fusion.
- Uncoating: Capsid removal liberates the viral genome by using cellular factors.
- Biosynthesis: Synthesis of mRNA and replication of viral genome using host cell machinery.
- Assembly: Viral proteins and genomes coalesce into new virion particles.
- Release: Non-enveloped viruses lead to cell lysis, while enveloped viruses mature by budding without necessarily killing the host cell.
-
The one-step growth curve represents how time affects infectious virus production, with an eclipse phase when new infectious particles are undetectable.
Viral Tropism and Host Specificity
- Viral ligands (attachment proteins) interact with cellular receptors to determine host range and tissue tropism.
- Changes in receptor usage can lead to broader host ranges and novel diseases; Canine Parvovirus serves as a case study.
- Key stages in viral replication such as attachment, penetration, and biosynthesis are vulnerable to antibody interference, blocking the infection process.
Pathogenicity and Virulence Factors
- Viral fusion proteins and protease activation are critical in influencing tissue tropism and pathogenicity in avian influenza viruses, differentiating high-pathogenic from low-pathogenic strains.
RNA Virus Replication and Mutations
- All viruses must produce positive (+) sense mRNA for their proteins to be synthesized by host ribosomes.
- RNA viruses utilize distinct strategies, like RNA-dependent RNA synthesis or reverse transcription, to generate mRNA.
- The absence of proofreading mechanisms in RNA viruses leads to higher mutation rates and genetic diversity.
- Segmented genomes allow for reassortment between different viruses, contributing to viral adaptability and evolution.
Therapeutic Targets
- Viral proteins essential for replication present promising targets for antiviral development, as they are specific to viruses and avoid harming host cells.### Antiviral Therapeutics
- RdRp, RT, and DNA viral polymerases are unique to viruses and serve as prime targets for antiviral drugs.
- Viral proteases are crucial for processing viral polyproteins during biosynthesis, making them key targets for antiviral treatment.
Virus-Cell Interactions
- Susceptible Cells: Have specific receptors for viral attachment, but do not guarantee productive viral infection.
- Permissive Cells: Support complete viral replication beyond mere attachment; influenced by the host's internal biochemistry.
- Productive Infection: Occurs when a cell is both susceptible and permissive, leading to the generation of new infectious viral particles.
- Abortive Infection: Results when a cell is susceptible but not permissive, failing to produce viral progeny.
Cytopathic Effects (CPE)
- CPE indicates morphological changes in host cells caused by viral infections, detectable via light microscopy.
- CPE manifestations include cytoskeletal disruption, syncytia formation, necrosis, apoptosis, and lysis, with cell rounding preceding lysis.
- Certain CPE are virus-specific, aiding in diagnostics; for instance, syncytial cell formation is associated with several virus families.
Viral Latency and Tumor Development
- Viral Latency: Refers to the presence of a virus without replication, leading to no observable cellular effects.
- DNA viruses can drive tumor development by inactivating tumor suppressor genes, binding growth factor receptors, and producing transcription factors.
- Retroviruses influence tumor development through mechanisms such as gene acquisition, cellular gene activation, and stimulation of signaling pathways.
Viral Pathogenesis
- Pathogenicity: Qualitative measure of a virus's ability to cause disease; determined by both virus and host characteristics.
- Virulence: Quantitative measure of pathogenicity, focusing solely on the virus's severity.
Disease Management and Transmission
- Management practices to maintain a larger “underwater portion of the iceberg” include vaccination, good hygiene, nutrition, and minimizing stress.
- The virulence of a virus affects clinical outcomes; more virulent infections result in more severe disease manifestations.
Factors Influencing Viral Infection Outcomes
- Viral infection outcomes depend on virus genetics, exposure dose, and host characteristics such as age, immune status, nutritional health, and genetic makeup.
Modes of Viral Transmission
- Horizontal Transmission: Viruses enter through mucosal surfaces or skin; can lead to iatrogenic (medical procedure-related) transmission.
- Vertical Transmission: Occurs from dam to offspring, potentially leading to abortion or congenital diseases.
Transient vs. Persistent Infections
- Transient Infections: Characterized by complete clearance of the virus within a short duration, following self-limiting mechanisms controlled by the immune system.
- Persistent Infections: Virus remains in the host and may cause variable disease severity, often with immune evasion strategies in play.
Mechanisms of Viral Persistence
- Viruses employ tactics like evasion of the immune response, immune tolerance, tissue-specific infection, and restricted gene expression to persist in the host.
Immune System Evasion
- Viruses can induce ineffective antibodies, change neutralizing antigens, and interfere with antigen presentation to evade the adaptive immune response.
Differences Between Localized and Systemic Infections
- Localized Infections: Short incubation period, virus replicates near the entry site, and shedding occurs from the same organ.
- Systemic Infections: Longer incubation, extensive spreading via lymphatic and hematogenous routes, peak viremia coinciding with clinical signs.
Core Temperature and Viral Replication
- Changes in body temperature can influence the site of viral replication; cooler areas may promote localized replication, as seen in respiratory or dermal infections.
Resolution of Viral Infection
- Termination factors include depletion of susceptible cells (crucial for localized infections) and the immune response (adaptive response predominates in systemic infections).
Diagnostic Testing for Viral Infections
- Differences exist in serological response based on mechanisms of persistence; immunologic tolerance often results in no antibodies, whereas latency yields minimal antibody production despite low antigen levels.### Timing Differences: Localized vs Systemic Infections
- Peak viral replication occurs around days 3-4 for localized infections and days 8-9 for systemic infections.
- Innate immune response is initiated at day 2 in localized infections, while adaptive immune response begins around day 9-10 in systemic infections.
- Clinical signs of localized infections appear around day 2, while systemic infections show signs between 8-12 days post-infection.
- During localized infections, diagnostic samples should be collected around days 2-4, whereas, for systemic infections, they are collected around days 8-9.
Host Defense Systems Against Viral Infections
- 1st line of defense: Physical and biochemical barriers at body surfaces (skin, mucociliary clearance, acidity, etc.).
- 2nd line of defense: Innate immune response, a generalist response activated rapidly upon pathogen recognition.
- 3rd line of defense: Adaptive immune response, taking days to weeks to develop and resulting in immunological memory.
Detection of Viral Infections
- Innate immune system identifies viruses through pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs).
- PRR binding triggers a signaling cascade leading to type I interferons (IFNs) and proinflammatory cytokines induction.
Role of Type I Interferons
- Type I IFNs (alpha and beta) are rapidly produced within 3-4 hours after viral infection.
- They protect neighboring uninfected cells by inducing antiviral responses, but do not protect already infected cells.
- Host-specific nature ensures selective action against viral infections.
Fever Response During Viral Infection
- Proinflammatory cytokines released from infected cells lead to febrile responses, which inhibit viral replication and enhance defense mechanisms.
- Symptoms associated with fever include malaise and flu-like sensations.
- Caution advised when using anti-pyretics; they should only be used at dangerously high fever levels.
NK Cells and Phagocytes in Viral Infections
- NK cells and phagocytes respond quickly (2-3 days) and are not antigen-specific.
- NK cells destroy virus-infected cells, while phagocytes engulf and degrade viruses.
- Both cells release cytokines that stimulate adaptive immune response.
Humoral and Cell-Mediated Immune Responses
- B lymphocytes produce antibodies, while T lymphocytes (helper and cytotoxic) play distinct roles in enhancing and activating immune response.
- Humoral immunity targets extracellular viruses, whereas cell-mediated immunity addresses intracellular viruses.
Antibody-Mediated Host Defense Mechanisms
- Neutralization: Antibodies prevent virus attachment and entry into cells.
- Opsonization and Phagocytosis: Antibodies facilitate virus uptake by phagocytes.
- Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Killing of virally infected cells through specific antibodies binding viral antigens.
Mechanisms of Virus Neutralization by Antibodies
- Antibodies may block ligand-receptor interactions, inhibit penetration/uncoating, aggregate viral particles, or lead to lysis via complement activation.
Role of Cytotoxic T Cells
- Cytotoxic T lymphocytes (CTLs) recognize viral peptides presented by MHC Class I and induce apoptosis of infected cells.
- Helper T cells assist in the activation of CTLs and enhance the overall immune response.
Viral Strategies to Evade Immune Response
- Viruses adopt mechanisms like antigenic variation, preventing apoptosis, evasion through latency, modulating MHC expression, and invoking immune cell destruction.
Immune Response Pathogenesis
- In certain infections (e.g., FIP), immune response products can lead to disease symptoms, such as vasculitis from immune complex formation.
Vaccination Goals and Strategies
- Vaccination aims to prevent/reduce disease and transmission of viral infections.
- Vaccines are complemented by quarantine and disinfection for effective control.
Characteristics of Attenuated Vaccines
- Attenuated vaccines are derived from avirulent strains that stimulate protective immunity while retaining some viral characteristics and replicative capacity.
Types of Viral Gene Product Vaccines
- Types include protein subunit vaccines, virus-like particles (VLP), and DNA/RNA vaccines coding for protective antigens.
DIVA Vaccines Advantages
- DIVA vaccines allow differentiation between infected and vaccinated animals through specific markers, improving monitoring and control measures.
Mixing Vaccines Caution
- Mixing viable virus vaccines with inactivated or subcomponent vaccines can reduce efficacy due to unintended immune responses.
Replicating vs Non-Replicating Vaccines
- Replicating vaccines provide strong immunity but may revert to virulence, while non-replicating vaccines are safer but less effective.
Barriers to Effective Antiviral Drug Development
- Antiviral drugs must be safe and effective, with challenges including target specificity, early treatment needs, issues with viral replication in vitro, and high costs.
Modes of Action for Antiviral Drugs
- Direct-acting antivirals target stages of virus replication, including uncoating, replication, release, and protein synthesis to inhibit viral lifecycle efficiently.
Introduction to Viruses
- Six key impacts of viruses include causing significant animal diseases, economically important exotic diseases, zoonotic diseases, inducing cancers, triggering newly recognized diseases, and serving as vectors in biological studies.
- Viral transmission is efficient, characterized by high titers, environmental stability, and various transmission routes.
- RNA viruses exhibit high mutation rates, potentially causing significant disease or enabling cross-species infections.
- Viruses evade host defenses through mechanisms such as latency and antigenic variation, leading to persistence and potential for new infections.
- Unlike bacteria, viruses are not affected by common antibiotics and antiviral drugs are limited in availability.
Sources of Viral Infections
- Primary infection can spread through reinfection, mitigated by isolating infected hosts.
- Zoonotic transmission is reduced by minimizing interspecies interactions.
- Environmental infection severity can be lessened through sanitation and decontamination practices.
- Persistently infected hosts may require antiviral treatment or supportive care.
- Vector-borne transmission can be alleviated by implementing preventative measures.
Virus Structure and Classification
- Viral genomes can be RNA or DNA, with variations such as linear or circular, single-stranded or double-stranded, and can vary in size from 2kb to over 200kb.
- Capsids are protective protein shells, while envelopes are lipid membranes derived from host cells containing viral glycoproteins.
- Enveloped viruses are sensitive to heat, oxidation, freezing/thawing, desiccation, and detergents, making them easier to control through sanitation.
- Capsid proteins serve as optimal targets for serological testing and vaccine development due to their conservation across virus variants.
Viral Replication
-
Six key steps of viral replication:
- Attachment: Virion binds to host cell using viral attachment proteins and host receptors.
- Penetration: Virus crosses the host cell membrane via direct penetration or membrane fusion.
- Uncoating: Capsid removal liberates the viral genome by using cellular factors.
- Biosynthesis: Synthesis of mRNA and replication of viral genome using host cell machinery.
- Assembly: Viral proteins and genomes coalesce into new virion particles.
- Release: Non-enveloped viruses lead to cell lysis, while enveloped viruses mature by budding without necessarily killing the host cell.
-
The one-step growth curve represents how time affects infectious virus production, with an eclipse phase when new infectious particles are undetectable.
Viral Tropism and Host Specificity
- Viral ligands (attachment proteins) interact with cellular receptors to determine host range and tissue tropism.
- Changes in receptor usage can lead to broader host ranges and novel diseases; Canine Parvovirus serves as a case study.
- Key stages in viral replication such as attachment, penetration, and biosynthesis are vulnerable to antibody interference, blocking the infection process.
Pathogenicity and Virulence Factors
- Viral fusion proteins and protease activation are critical in influencing tissue tropism and pathogenicity in avian influenza viruses, differentiating high-pathogenic from low-pathogenic strains.
RNA Virus Replication and Mutations
- All viruses must produce positive (+) sense mRNA for their proteins to be synthesized by host ribosomes.
- RNA viruses utilize distinct strategies, like RNA-dependent RNA synthesis or reverse transcription, to generate mRNA.
- The absence of proofreading mechanisms in RNA viruses leads to higher mutation rates and genetic diversity.
- Segmented genomes allow for reassortment between different viruses, contributing to viral adaptability and evolution.
Therapeutic Targets
- Viral proteins essential for replication present promising targets for antiviral development, as they are specific to viruses and avoid harming host cells.### Antiviral Therapeutics
- RdRp, RT, and DNA viral polymerases are unique to viruses and serve as prime targets for antiviral drugs.
- Viral proteases are crucial for processing viral polyproteins during biosynthesis, making them key targets for antiviral treatment.
Virus-Cell Interactions
- Susceptible Cells: Have specific receptors for viral attachment, but do not guarantee productive viral infection.
- Permissive Cells: Support complete viral replication beyond mere attachment; influenced by the host's internal biochemistry.
- Productive Infection: Occurs when a cell is both susceptible and permissive, leading to the generation of new infectious viral particles.
- Abortive Infection: Results when a cell is susceptible but not permissive, failing to produce viral progeny.
Cytopathic Effects (CPE)
- CPE indicates morphological changes in host cells caused by viral infections, detectable via light microscopy.
- CPE manifestations include cytoskeletal disruption, syncytia formation, necrosis, apoptosis, and lysis, with cell rounding preceding lysis.
- Certain CPE are virus-specific, aiding in diagnostics; for instance, syncytial cell formation is associated with several virus families.
Viral Latency and Tumor Development
- Viral Latency: Refers to the presence of a virus without replication, leading to no observable cellular effects.
- DNA viruses can drive tumor development by inactivating tumor suppressor genes, binding growth factor receptors, and producing transcription factors.
- Retroviruses influence tumor development through mechanisms such as gene acquisition, cellular gene activation, and stimulation of signaling pathways.
Viral Pathogenesis
- Pathogenicity: Qualitative measure of a virus's ability to cause disease; determined by both virus and host characteristics.
- Virulence: Quantitative measure of pathogenicity, focusing solely on the virus's severity.
Disease Management and Transmission
- Management practices to maintain a larger “underwater portion of the iceberg” include vaccination, good hygiene, nutrition, and minimizing stress.
- The virulence of a virus affects clinical outcomes; more virulent infections result in more severe disease manifestations.
Factors Influencing Viral Infection Outcomes
- Viral infection outcomes depend on virus genetics, exposure dose, and host characteristics such as age, immune status, nutritional health, and genetic makeup.
Modes of Viral Transmission
- Horizontal Transmission: Viruses enter through mucosal surfaces or skin; can lead to iatrogenic (medical procedure-related) transmission.
- Vertical Transmission: Occurs from dam to offspring, potentially leading to abortion or congenital diseases.
Transient vs. Persistent Infections
- Transient Infections: Characterized by complete clearance of the virus within a short duration, following self-limiting mechanisms controlled by the immune system.
- Persistent Infections: Virus remains in the host and may cause variable disease severity, often with immune evasion strategies in play.
Mechanisms of Viral Persistence
- Viruses employ tactics like evasion of the immune response, immune tolerance, tissue-specific infection, and restricted gene expression to persist in the host.
Immune System Evasion
- Viruses can induce ineffective antibodies, change neutralizing antigens, and interfere with antigen presentation to evade the adaptive immune response.
Differences Between Localized and Systemic Infections
- Localized Infections: Short incubation period, virus replicates near the entry site, and shedding occurs from the same organ.
- Systemic Infections: Longer incubation, extensive spreading via lymphatic and hematogenous routes, peak viremia coinciding with clinical signs.
Core Temperature and Viral Replication
- Changes in body temperature can influence the site of viral replication; cooler areas may promote localized replication, as seen in respiratory or dermal infections.
Resolution of Viral Infection
- Termination factors include depletion of susceptible cells (crucial for localized infections) and the immune response (adaptive response predominates in systemic infections).
Diagnostic Testing for Viral Infections
- Differences exist in serological response based on mechanisms of persistence; immunologic tolerance often results in no antibodies, whereas latency yields minimal antibody production despite low antigen levels.### Timing Differences: Localized vs Systemic Infections
- Peak viral replication occurs around days 3-4 for localized infections and days 8-9 for systemic infections.
- Innate immune response is initiated at day 2 in localized infections, while adaptive immune response begins around day 9-10 in systemic infections.
- Clinical signs of localized infections appear around day 2, while systemic infections show signs between 8-12 days post-infection.
- During localized infections, diagnostic samples should be collected around days 2-4, whereas, for systemic infections, they are collected around days 8-9.
Host Defense Systems Against Viral Infections
- 1st line of defense: Physical and biochemical barriers at body surfaces (skin, mucociliary clearance, acidity, etc.).
- 2nd line of defense: Innate immune response, a generalist response activated rapidly upon pathogen recognition.
- 3rd line of defense: Adaptive immune response, taking days to weeks to develop and resulting in immunological memory.
Detection of Viral Infections
- Innate immune system identifies viruses through pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs).
- PRR binding triggers a signaling cascade leading to type I interferons (IFNs) and proinflammatory cytokines induction.
Role of Type I Interferons
- Type I IFNs (alpha and beta) are rapidly produced within 3-4 hours after viral infection.
- They protect neighboring uninfected cells by inducing antiviral responses, but do not protect already infected cells.
- Host-specific nature ensures selective action against viral infections.
Fever Response During Viral Infection
- Proinflammatory cytokines released from infected cells lead to febrile responses, which inhibit viral replication and enhance defense mechanisms.
- Symptoms associated with fever include malaise and flu-like sensations.
- Caution advised when using anti-pyretics; they should only be used at dangerously high fever levels.
NK Cells and Phagocytes in Viral Infections
- NK cells and phagocytes respond quickly (2-3 days) and are not antigen-specific.
- NK cells destroy virus-infected cells, while phagocytes engulf and degrade viruses.
- Both cells release cytokines that stimulate adaptive immune response.
Humoral and Cell-Mediated Immune Responses
- B lymphocytes produce antibodies, while T lymphocytes (helper and cytotoxic) play distinct roles in enhancing and activating immune response.
- Humoral immunity targets extracellular viruses, whereas cell-mediated immunity addresses intracellular viruses.
Antibody-Mediated Host Defense Mechanisms
- Neutralization: Antibodies prevent virus attachment and entry into cells.
- Opsonization and Phagocytosis: Antibodies facilitate virus uptake by phagocytes.
- Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Killing of virally infected cells through specific antibodies binding viral antigens.
Mechanisms of Virus Neutralization by Antibodies
- Antibodies may block ligand-receptor interactions, inhibit penetration/uncoating, aggregate viral particles, or lead to lysis via complement activation.
Role of Cytotoxic T Cells
- Cytotoxic T lymphocytes (CTLs) recognize viral peptides presented by MHC Class I and induce apoptosis of infected cells.
- Helper T cells assist in the activation of CTLs and enhance the overall immune response.
Viral Strategies to Evade Immune Response
- Viruses adopt mechanisms like antigenic variation, preventing apoptosis, evasion through latency, modulating MHC expression, and invoking immune cell destruction.
Immune Response Pathogenesis
- In certain infections (e.g., FIP), immune response products can lead to disease symptoms, such as vasculitis from immune complex formation.
Vaccination Goals and Strategies
- Vaccination aims to prevent/reduce disease and transmission of viral infections.
- Vaccines are complemented by quarantine and disinfection for effective control.
Characteristics of Attenuated Vaccines
- Attenuated vaccines are derived from avirulent strains that stimulate protective immunity while retaining some viral characteristics and replicative capacity.
Types of Viral Gene Product Vaccines
- Types include protein subunit vaccines, virus-like particles (VLP), and DNA/RNA vaccines coding for protective antigens.
DIVA Vaccines Advantages
- DIVA vaccines allow differentiation between infected and vaccinated animals through specific markers, improving monitoring and control measures.
Mixing Vaccines Caution
- Mixing viable virus vaccines with inactivated or subcomponent vaccines can reduce efficacy due to unintended immune responses.
Replicating vs Non-Replicating Vaccines
- Replicating vaccines provide strong immunity but may revert to virulence, while non-replicating vaccines are safer but less effective.
Barriers to Effective Antiviral Drug Development
- Antiviral drugs must be safe and effective, with challenges including target specificity, early treatment needs, issues with viral replication in vitro, and high costs.
Modes of Action for Antiviral Drugs
- Direct-acting antivirals target stages of virus replication, including uncoating, replication, release, and protein synthesis to inhibit viral lifecycle efficiently.
Introduction to Viruses
- Viruses significantly impact animals, humans, and scientific research through disease causation, economic impact, zoonotic potential, cancer induction, emergence of novel diseases, and serving as vectors for biological processes.
- Virus transmission is highly efficient, capable of reaching high titers, being environmentally stable, and utilizing varied transmission routes.
- High genomic mutation rates in RNA viruses enable strain development, host species-jumping, and evasion of immune defenses.
- Viruses persist within hosts, contributing to reinfection risks, with limited tools available for antiviral therapy.
- Key virus sources impacting animals include primary infections, zoonotic transfers, environmental infections, persistently infected hosts, and vector-borne transmission; mitigation strategies involve isolation, reduced interspecies interactions, sanitation, and antiviral treatments.
- Viruses exhibit unique structures with capsids (protein shells) and envelopes (lipid membranes); they differ from bacteria in replication, genome composition, and the inability to be treated with antibiotics.
- Viruses are extremely small, typically measured in nanometers, and require electron microscopy for visualization.
Virus Structure and Classification
- Viral genomes vary in type (RNA or DNA), structure (linear or circular), strandedness (single or double), size (2kb to >200kb), and polarity (+, -, or ambisense).
- Capsids provide protective protein shells for viral nucleic acids, while envelopes include a lipid bilayer and glycoproteins derived from host cells.
- Enveloped viruses are sensitive to heat, oxidation, freezing/thawing, desiccation, and detergents, which can be exploited for infection control in veterinary medicine.
- Capsid proteins serve as optimal targets for serological testing and vaccine development due to their conserved nature and immunogenic properties.
- Serotype defines a virus group identifiable by antigenic properties, with novel serotypes emerging from mutations or recombination affecting viral characteristics and potential consequences.
Viral Replication
- Key steps of viral replication: attachment, penetration, uncoating, biosynthesis, assembly, and release, with specific processes occurring at each stage.
- The eclipse phase denotes a period during viral replication when the virus is not detectable in measurable quantities, as it undergoes uncoating and protein synthesis within the host cell.
- Viral ligand (VAP) binds to host cell receptors, influencing tissue and host tropism, critical for understanding viral infection dynamics.
- Changes in receptor usage can lead to expanded host or tissue ranges, illustrated by the emergence of Canine Parvovirus.
- Antibodies can interfere at multiple stages of viral replication, particularly during attachment and penetration.
Viral Fusion and Proteolytic Activation
- Fusion proteins facilitate viral entry by inserting into cellular membranes, influenced by protease cleavage necessary for activation.
- Low pathogenic avian influenza (LPAI) affects limited tissue due to local protease distribution; high pathogenic avian influenza (HPAI) involves widespread protease distribution leading to severe disease.
Targeting Viral Replication
- Positive sense mRNA production is essential as it serves as a template for viral protein synthesis.
- RNA viruses employ RNA-dependent mechanisms for mRNA synthesis, making them prone to higher mutation rates due to lack of proofreading.
- Segmented genomes allow for genetic reassortment, providing adaptability and potential for new strains.
- Viral proteins critical for replication present excellent targets for antiviral development, minimizing effects on host cellular processes.### Antiviral Therapeutics
- RdRp, RT, and DNA viral polymerases are unique viral enzymes targeted by antiviral drugs.
- Viral proteases are crucial for processing viral polyproteins during biosynthesis and are also targets for antiviral medications.
Virus-Cell Interactions
- Susceptible cells have the correct receptors for viral attachment but do not ensure the production of infectious virus.
- Permissive cells support complete viral replication beyond attachment due to favorable internal biochemistry.
- Productive infection leads to the creation of new infectious viral particles.
- Abortive infection occurs when no progeny virions are produced despite susceptibility, indicating a lack of permissiveness.
- Cytopathic effect (CPE) involves visible cellular changes due to viral infections, identifiable under light microscopy, including cell lysis, necrosis, and syncytia formation.
Types of Infections
- Cytolytic infections cause cell death and characterized CPE can assist in virus diagnosis.
- Viral latency refers to viruses being present without replication, implying the absence of observable cellular effects.
- DNA viruses can promote tumor development by producing oncoproteins that inactivate tumor suppressors, activate growth factor receptors, and influence transcription.
Tumor Development Mechanisms
- Retroviruses can cause tumors through:
- Gene acquisition via transduction
- Activation of cellular genes through insertional or trans-activation
- Signal transduction activation, prompting cell growth.
Viral Pathogenesis
- Pathogenicity indicates a virus's ability to cause disease, while virulence measures disease severity quantitatively.
- A higher virus virulence shifts disease outcomes, leading to more severe clinical signs.
- Key factors influencing viral infection outcomes include genetic virus features, exposure dose, age, immune status, concurrent infections, nutritional status, and genetics.
Viral Transmission Factors
- DEED principles (Dose, Envelope, Environment, Distance) guide viral transmission risk assessment.
- Viruses enter hosts primarily via mucosal surfaces, skin, and through vertical transmission from mother to offspring.
Infections: Transient vs Persistent
- Transient infections are usually cleared by the immune system with a short duration, while persistent infections are maintained and may lead to variable disease severity.
- Viral persistence is maintained via mechanisms like immune evasion, tolerance, and restricted gene expression.
Immune Evasion Tactics
- Viruses may produce non-neutralizing antibodies, undergo antigenic variation, or disrupt the antigen presentation pathway to evade the immune response.
Diagnostic Testing Differences
- For persistent infections via immunologic tolerance, no antibodies are produced, while latently infected individuals may produce few antibodies due to limited viral gene expression.
Localized vs Systemic Infections
- Localized infections replicate at or near entry points and exhibit short incubation periods, while systemic infections spread throughout the body, have longer incubation periods, and peak serum viral titers.
- Primary viremia is typically subclinical; secondary viremia has detectable viral levels and correlates with clinical disease onset.
Factors Influencing Infection Outcomes
- The outcome of infections is affected by factors determining whether a virus remains localized or becomes systemic, including the release direction of viral particles and the susceptibility of macrophages.
Impact of Hypothermia
- Hypothermia can allow viruses to replicate in cooler areas of the body, potentially shifting infection sites and causing complications, such as pneumonia from Feline herpesvirus in young animals.
Termination of Viral Infections
- Active viral infections terminate primarily through the depletion of susceptible cells and the immune response, with resolution factors varying in importance between localized and systemic infections.### Timing Differences in Infections
- Localized vs Systemic Infections: Localized infections peak viral replication around days 3-4, while systemic infections peak around days 8-9.
- Immune Responses: Innate immune response activation occurs around day 2 for localized infections; systemic infections trigger adaptive responses by day 9 or 10.
- Clinical Signs: Signs of localized infections start around day 2, with significant signs by day 4. Systemic infections show symptoms 8-12 days post-infection.
- Diagnostic Timing: Samples for localized infections are optimal during days 2-4, while samples for systemic infections should be collected around days 8-9.
Host Defense Systems Against Viral Infections
- Physical and Biochemical Barriers: These include skin, mucociliary clearance, acid, bile, and natural inhibitors; they repel many pathogens.
- Innate Immune Response: A generalist response that activates rapidly upon pathogen recognition and induces adaptive immune responses.
- Adaptive Immune Response: Antigen-specific and may take days to weeks to develop, resulting in immunological memory.
Detection and Activation of Immune Response
- Detection Mechanism: Viruses are detected by pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs).
- Type I Interferons: Produced by almost all cells in response to infection, these cytokines act rapidly, inducing antiviral responses in neighboring uninfected cells and helping to slow down the infection.
Fever and Immune Response
- Proinflammatory Cytokines: These cytokines lead to fever and increase defensive activities, which contribute to flu-like symptoms.
- Benefits of Fever: Inhibits viral replication, increases blood flow, and enhances inflammatory responses; anti-pyretics should only be used for dangerously high fevers.
Role of Immune Cells
- NK Cells: Quickly respond to viral infections, killing infected cells and secreting cytokines that stimulate adaptive responses.
- Phagocytes: Involved in degrading viruses and facilitating faster immune responses by clearing viral particles.
Adaptive Immune Response
- B and T Lymphocytes: B cells produce antibodies while helper T cells activate B cells and cytotoxic T lymphocytes (CTLs), which kill infected cells.
- Immune Responses: Humoral immunity targets extracellular viruses, while cell-mediated immunity targets intracellular viruses.
Antibody-Mediated Host Defense Mechanisms
- Neutralization: Antibodies bind to viruses, blocking infection and preventing penetration.
- Opsonization and Phagocytosis: Antibodies facilitate the uptake of viruses by phagocytic cells.
- Antibody-Dependent Cellular Cytotoxicity (ADCC): Specific antibodies mark infected cells for destruction by immune cells.
Mechanisms of Virus Neutralization
- Blocking Interactions: Antibodies prevent viruses from binding and entering cells, and can induce aggregation of virus particles.
- Inhibition and Lysis: Antibodies can stabilize viral structures and, in combination with complement, lead to lysis of viruses.
CTLs and Helper T Cells' Roles
- Cytotoxic T Lymphocytes (CTLs): Recognize viral antigens and induce apoptosis in infected cells through perforins and granzymes.
- Helper T Cells: Activate CTLs and enhance immune responses through cytokine secretion.
Viral Evasion Strategies
- Antigenic Variation: Viruses may change their surface antigens to escape immune recognition.
- Inhibition of Immune Functions: They can prevent apoptosis, modulate MHC expression, and target cytokines.
Immune Response and Pathogenesis
- Feline Infectious Peritonitis (FIP): Caused by the immune response to feline enterovirus mutation leading to tissue damage due to immune complex formation.
Vaccination Goals and Characteristics
- Goals of Vaccination: Aim to prevent disease and reduce viral transmission.
- Attenuated Vaccines: Should induce protective immunity with reduced virulence, achieved through natural strains or experimental mutations.
Vaccine Types
- Gene Product Vaccines: Include subunit, VLP, DNA, and RNA vaccines, differing from whole virus vaccines.
- DIVA Vaccines: Differentiate infected from vaccinated animals using specific gene deletions.
Antiviral Drug Development Challenges
- Safety Issues: Creating effective but non-toxic antiviral drugs is challenging due to viral dependency on host cell machinery.
- Narrow Target Specificity: Limited options for broad-acting antivirals necessitate accurate viral diagnosis.
Antiviral Drug Mechanisms
- Direct Action: Antivirals target various stages of viral life cycles, such as uncoating (e.g., amantadine) and replication (e.g., nucleoside analogs like acyclovir).
- Release Inhibition: Neuraminidase inhibitors, such as Tamiflu, block viral release, while protease inhibitors like Paxlovid target viral protein synthesis.
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This quiz covers Chapter 1 of Veterinary Virology, focusing on the introduction to viruses. It highlights the significant impacts of viruses on domestic animals, humans, and agriculture. Explore the diseases caused by viruses and their relevance to public health.