Virus Structure and Host Range

• Viruses are composed of a genome, either DNA or RNA, surrounded by a protein coat called a capsid
• Some viruses possess an outer layer called an envelope
• Viruses can only reproduce within a host cell
• Viruses hijack the host cell's machinery, such as ribosomes and enzymes, to create copies of themselves
• Viruses must attach to and enter a host cell to reproduce
• Antibiotics are ineffective against viruses
• Viruses are acellular pathogens
• Viruses are obligate intracellular parasites, which means they have to reproduce inside a host cell

Host Range

• Host range describes the spectrum of cell types and host species a virus can infect
• Host range depends on the virus's ability to attach to the host cell
• Viruses can cross host species barriers, like a bird virus infecting humans or cows, often due to antigenic drift
• "Spillover" happens when a virus with a non-human animal host range becomes infectious to humans
• Bacteriophages are viruses that infect bacteria

Virion

• Virion is the complete virus particle outside the host cell

Virus components

Genetic Material

• Genetic material consists of DNA or RNA, but never both

Capsid

• The capsid is a protein coat that surrounds and protects the nucleic acid
• Capsid is composed of capsomeres, which are protein subunits that interlock
• All viruses have a capsid
• A capsid helps with attachment
• The capsid's ability to change helps viruses avoid the host immune cell response (antigenic drift)

Envelope

• The envelope is a phospholipid membrane layer surrounding most viruses, derived from the host cell
• Envelopes consist of a combination of protein lipids and CHO (carbohydrates)
• Some animal viruses take part of the host cell plasma membrane, which becomes part of the envelope
• Not all viruses have an envelope
• An envelope helps with attachment and surrounds the capsid
• The envelope's composition can help viruses invade the host immune system (antigenic drift)

Spikes

• Spikes are protein structures extending outward from some viruses
• Spikes allow viruses to attach and enter the cell, detaching during release

Antigenic Drift

• Antigenic drift occurs when the composition of the capsid or envelope changes, resulting in mutations of the viral genome
• Antigenic drift helps viruses evade the host immune response, making it hard for the host to recognize the virus
• Viruses can infect an individual more than once due to antigenic drift

Viral Genome

• The viral genome can be DNA or RNA, but never both
• Viral genome can be linear or circular and single-stranded or double-stranded
• Genomes consist of one or several segments, not chromosomes
• Viruses are very small compared to chromosomes
• They carry only a few genes (capsid proteins, some critical viral enzymes) and use host cell machinery for reproduction

Viral Taxonomy

• Taxonomy classifies and names viruses
• The species naming scheme is not used for viral taxonomy
• Order names end in -viriaies, family names end in -virade, Genus names end in -virus, and strain is identified in alphanumeric
• Viruses infecting bacteria can make thousands of copies of themselves after invading host cells
• Phage infection of bacteria can make bacteria more pathogenic to humans (lysogen)
• Phages can be used to treat bacterial infections (phage therapy)

Bacteriophage Multiplication

Lytic Phages

• Lytic phages are bacteriophages with only a lytic cycle
• After invading a host cell, the phage makes many copies of itself immediately
• It lyse the host bacterium for the mature copies to leave, resulting in cell death by rupture
• Lysis causes cell death by rupture

Lysogenic Phages

• Lysogenic phages are bacteriophages that have lysogenic and lytic cycles
• The phage does not immediately make more copies of itself
• The viral genome integrates with the bacterial genome

The Lytic Cycle

1. Attachment: Phage attaches to host cell.
2. Penetration: Phage penetrates the host cell and injects DNA.
3. Biosynthesis: Phage DNA directs the synthesis of viral components by the host cell.
4. Maturation: Viral components are assembled into virions.
5. Release: The host cell lyses, and new virions are released

The Lysogenic Cycle

1. Phage attaches to host cell and injects DNA.
2. Phage DNA circularizes and enters the lytic or lysogenic cycle.
3. Phage DNA integrates within the bacterial chromosome by recombination, thus becoming a prophage.
4. The lysogenic bacterium then reproduces normally

Specialized Transduction

• Specialized transduction occurs when some bacterial genes are excised with viral DNA during the transition from the lysogenic to the lytic cycle
• Recombinant phages can later infect other bacteria
• Process:*

1. A prophage exists in a galactose-using host
2. The phage genome excises, carrying the adjacent gal gene from the host
3. The phage matures and cell lyses, releasing phage carrying gal gene
4. The phage infects a cell that cannot utilize galactose
5. Along with the prophage, the bacterial gal gene integrates into the new host's DNA
6. The lysogenic cell can now metabolize galactose

Phage Conversion

• Phage conversion bacterium gets new properties from expressing genes of a prophage of a lysogen phage
• It can make the bacterium more dangerous and contain genes for toxins or antibiotic resistance

Phage Therapy

• Phage therapy is the use of bacteriophages to treat bacterial infections
• Lytic phages are preferred due to their faster lysis (death) of bacteria
• Lysogenic phages take longer to kill bacteria due to their length in the lysogenic cycle
• A lytic phage provides effectiveness if it will infect the bacterium
• Phage therapy is used in cases of multi-drug-resistant bacterial infections
• Phage therapy is not widely used

Animal Virus Multiplication

DNA Viruses

• DNA viruses have a single-stranded or double-stranded DNA genome
• Examples include herpes (HSV), Epstein–Barr, and Hep B (HBV)
• Process:*

1. Attachment to host cell
2. Entry into the host cell
3. Viral DNA enters the nucleus
4. Viral DNA is transcribed to viral mRNA and replicated to make more viral DNA
5. Viral mRNA is transcribed in the cytoplasm or rough ER to make viral proteins
6. New viral copies assemble, mature, and then leave the host cell

RNA Viruses (Non-retroviral)

• RNA viruses possess an RNA genome (single-stranded or double-stranded)
• Examples include COVID-19, Hep C, norovirus, and influenza
• Process:*

1. Attachment to host cells
2. Entry into the host cell
3. RNA-dependent RNA polymerase (encoded in the viral genome) reads viral RNA and makes new copies of viral RNA
4. Viral mRNA is translated to make viral proteins
5. New viral copies assemble, mature and then leave the host cell

Retroviruses

• Retroviruses are a type of RNA virus
• Process:*

1. Attachment to the host cell
2. Entry into the host cell
3. Reverse transcriptase – viral enzyme that reads viral RNA and makes viral DNA, occurring in the cytoplasm
4. Viral DNA then enters the nucleus of the host cell and integrates into chromosomal DNA of the host cell as a provirus
5. The provirus may remain in the host's chromosomal DNA before copies are made
6. Transcription of viral DNA and translation of viral mRNA result in creating new viral proteins
7. New viral copies assemble, mature, and then leave the host cell

• Viral DNA is "protected" once it integrates, avoiding detection by host immune cells
• The terms "viral copy," "virion," and "viral particle" are synonyms for "individual/ single virus"
• Viral genome viruses never need to enter the nucleus
• Viral RNA-dependent RNA polymerase makes more copies of the viral RNA genome (RNA -> RNA) occuring in the cytoplasm

Reverse Transcription

• Reverse transcription is performed by retroviruses
• Viral RNA genomes are reverse transcribed to viral DNA by viral reverse transcriptase
• Viral DNA then enters the host cell nucleus and integrates with the host genome (chromosome), and upon integration, it is called a "provirus"

Oncogenic Viruses

• Onco means cancer and genic means genesis/creation
• Oncogenic viruses are viruses that cause cancer
• Examples: some retroviruses, some adenoviruses, and HPV

Oncolytic Viruses

• Onco means cancer and lytic means lysis/rupture
• Oncolytic viruses lyse/rupture/kill cancer cells

Eclipse Period

• Eclipse period is the period during a viral infection
• During this period, the host cell has been infected and viral multiplication is in process but not yet complete, and no new mature viral copies (virions, viral particles) have been released by infected host cells

Types of Viral Infections

Acute

• Viral multiplication occurs quickly, so illness occurs quickly (after initial exposure).

Persistent

• Slow viral multiplication and a slow increase in viral copies are observed over a long period (years)
• There can be mild symptoms until the immune system is weakened
• Can cause cancer from HPV exposure, HIV, or Hepatitis

Latent

• Long period with virtually no viral multiplication/ no increase in viral copies
• It can be oncogenic, e.g., cancer from HPV
• Varicella virus lies dormant for years/decades after chickenpox and can eventually multiply again, causing shingles

Plant Viruses

• Plant viruses exist for every possible host, including plants

Viral Identification

• Seeing most viruses requires very advanced microscopy (e.g., electron microscopy) because they are very small
• An ELISA test (immunoassay) uses antibodies specific to certain viruses
• Cytopathic effects (damage to cells) can be observed, such as Negri bodies in neutral tissue in rabies infections

Viral Culture

• Growth is used for vaccine production and biotechnology/biogenesis
• It is much more challenging than standard bacterial culture
• Often, fertilized chicken eggs or living lab animal hosts are needed

Prions

• Prions are infectious proteins (host = humans, other animals)
• Prions cause transmissible spongiform encephalopathy, in other words, contagious holes in brain
• Prion diseases (all have severe neurological signs, symptoms, and fatal outcomes)
• Bovine Spongiform Encephalopathy (BSE) or Mad Cow Disease
• Variant Crendzfeldt-Jacob or vCJD - BSE in humans
• Kuru-canabolism is also a prion disease

Inactivating Prions

• A lot about prions is actively being researched
• Prions are tough to remove with filtration becasue they are very small
• They are unaffected by standard sterilization methods
• The best practice is to burn prion-contaminated materials to ash
• If burning is not doable, perform an aggressive sterilization procedure, but these sterilization methods have not been fully validated
• Once symptoms begin in rabies cases in humans, there is a 99% mortality/fatality rate
• Treatment must happen before symptoms begin to be effective

Terminology

Pathology

• Pathology studies disease

Etiology

• Etiology studies the cause of disease

Symptoms

• Symptoms are subjective changes in body function based on what the patient feels
• Symptoms are not visible to another person
• An example is when someone feels weak, tired, or malaise

Signs

• Signs are objective changes in body function
• Signs are visible to another person or healthcare professional
• An example is one's body temperature or bloodwork parameters

Pathogen

• A pathogen is a microorganism that causes disease

Pure Culture

• Pure culture grown in a lab using an agar or broth culture

Koch's Postulates

• Koch's postulates defines the germ theory of infectious disease, which is that infectious diseases are caused by microorganisms
• Postulates:*

1. The same pathogen must be present in every case of the disease.
   • Except, more than one different infectious disease may have related symptoms
2. The pathogen must be isolated from the host and grown in a pure culture.
   • Except, VBNC.
3. The pathogen from the pure culture must cause the disease when it's inoculated into a healthy, susceptible laboratory animal.
   • Except, humans differ
4. The pathogen must be isolated from the inoculated animal and be shown to be the original organism
   • Ethical exemption

Reservoirs of Infection

• Humans/human bodies
• Non-human animals
• Chronic carriers of infectious disease are individuals who have recovered but are still contagious
• Passive carriers don't experience the disease, but they spread the pathogen in a covered manner
• Nonliving reservoirs consist of soil and water
  • Soil reservoirs are chloridoids tetani and chloridoids botulism
  • Water reservoirs are untreated or poorly treated drinking water

Transmission

• Direct contact transmission happens when an infected host touches another host
• Droplet transmission is when droplets of bodily fluids, water, or other liquids that are contaminated with a pathogen are transmitted
  • These can be aerosolized droplets
• Fomite transmission is when an inanimate object is contaminated by an infected host, and then a susceptible host touches the object and becomes infected (fomite = contaminated inanimate object)
• Vectors are insects that transmit pathogens through a bite or blood-sucking event

Healthcare-Associated Infections (HAI)

• Requirements for HAI:*
• Pathogen must physically be present where a compromised host is present
• Transmission of some type must exist such as direct contact, fomite, or droplet

Emerging Infectious Diseases

• Emerging infectious diseases include Mpox and H5NI avian (bird) flu
• Before covid-19, that disease was still unknown
• Before the 1980s, HIV was unknown
• Sometimes pathogens reemerge because vaccination rates are low -e.g., measles, Polio, whooping cough, etc.

Epidemiology

• Epidemiology studies how a disease originates and spreads through a population to detect and control outbreaks

Case Reporting

• HCW are required by law to report cases of certain diseases, especially infectious ones
• Including STIs and other infectious diseases

Microbial Mechanism of Pathogenicity

• Mechanisms refer to different types of pathogens
• Pathogenicity refers to the ways pathogens cause infection and disease

Portals/Routers of Entry

• Eyes major portal of entry
• Mouth
• Respiratory tract - GI tract, digestive tract
• Skin - abrasion, injury, insect bites
• Urogenital tract - catheters, sexual activity
• Gastrointestinal tract
• Anus - sexual
• Mucous membranes can prevent infection that can line tracts and eyeballs
• Mucous membranes are a major portal of entry with defenses
• Mucous membranes will trap pathogens with a sticky mucus
• Improper sterile/aseptic technique can result in pathogen entry

Adhesion

• Attachment to host cell is the 1st step of infection
• Pathogen and host outer surface characteristics contribute to attachment
  • Can be surface proteins
  • Host cell recognition by pathogens
  • Host cells may trigger immune response when pathogens are detected

Phagocytes and Phagocytosis

• Phagocytes are host cells that can do phagocytosis
• Not all host cells are phagocytes
• During phagocytosis the a host cell engulfs pathogen with destroyal intent

Bacterial Mechanisms of Pathogenicity

Capsules

• Capsules a type of glycocalyx such as a slime layer
• Capsules consist of polysaccharides
  • Help the host cell with attachment
• Capsules help with phagocytosis because immune cells can't detect if there is foreign activity

Cell Wall Components

• Outermost surface of encapsulated Gram + bacteria
• M protein is found in group A Streptococci cells
  • Helps with attachment
  • Helps GAS cause impetigo, a strep throat that eats flesh

Mycolic Acid

• Found in cell walls of AF+ Bacteria (mycobacterium sp., nocardia sp, and tuberculosis)
  • Aids with resistance to lysis

Opa

• This Outer Membrane Protein aids with attachment to host cells
• Aids with opaque colonies

Bacterial enzymes that coagulate blood with fibrinogen

Kinases

• Aids in avoiding immune response

Hyaluronidase

• Breaking the hyaluronic acid component of skin to break tissue

collagenase

• Collagen is a protein found in skin to break tissue

IgA proteases

• Immunoglobin that reduces immune system responses

Antigenic variation

• Variations in dna alters host cells to destroy immune cells
• Bacteria changes outer surface

Host Penetration

• Invasions create holes in cell membranes that allow bacteria past defensive barriers
• Dramatic changes in cell engulfment

Traveling Inside

Flagella

• Transfer through host cells

Biofilms

• Membranes protect from the ECM and cell growth to help avoid immume response

Bacterial pathogen damage to host cells

Use nutrients

• Stealing nutrients from source or comforting iron with

Direct Damage

• Toxin and membrance damage

Toxin Production

• Endotoxins cause the spread from gram bacteria
• Exotoxins produced from bacteria

Exotoxins

• Exotoxins and diseases from bacteria require that the host and produce effects on the host body
• In response hosts produce antitoxins and cause toxin production
• Toxoids reduce toxins and stimulate toxin production
• Usually composed of proteins

Endotoxins

• Proteins produced from cells that cause symptoms with a response
• Cause issues and can become deadly
• Do not cause production

Plasmids

• Circular dna found inside the bacteria's chromosones
• Contains antibiotics to help environment
• Creates gene transfer

Lysogeny

Viral mechanisms of pathogenicity

• Viral multiplication happens within immune cells
• The outer surface mimics host cells
  • Ex: Rabis mimics a nerve cell for attack

Evading Host defenses

• Can destroy cells but can damage cell

Cytopathic effects

• Can create antibodies
• Syncta virus merges tissue

####Fungi Protocol:

Fungi Pathogenicity is toxic disease from toxins

• Produce spores (mold and grains)

Interferons

• Grow on animal body
• Varies

Mechanism of algai

• Toxic algae in water

How to exit:

• Sneezing
• Vomiting
• Fluids
• Tissue damage