Viral Infections & Pathogenesis PDF

Viral Infections & Pathogenesis Chapter 7 Classification of Medically Important Viruses The classification of viruses is based on chemical and morphologic criteria. Viral Pathogenesis The major components of the virus used in...

Viral Infections & Pathogenesis Chapter 7 Classification of Medically Important Viruses The classification of viruses is based on chemical and morphologic criteria. Viral Pathogenesis The major components of the virus used in The ability of viruses to cause disease can be viewed on two distinct levels: classification are: 1. The nucleic acid (its type and structure; - The changes that occur within DNA Vs RNA ) individual cells - Double- vs. single-stranded - Single or segmented pieces of nucleic acid - Positive (+) or negative (-) stranded RNA - The process that takes place in the - Complexity of genome infected patient. 2. The capsid (icosahedral Vs Helical ) 3. The envelope (Naked Vs Enveloped). Referred to as the HHAPPPy viruses: Herpes Hepadna Adeno Papova Parvo exception ssDNA Pox exception replicates in the cytoplasm and is not icosahedral but a box Most DNA viruses are double- stranded, show icosahedral symmetry, and replicate in the nucleus. Most RNA viruses are single- stranded (+ Vs -) sense, enveloped, show helical capsid symmetry, and replicate in the cytoplasm. Positive-sense RNA (+RNA) viruses have RNA that can be directly translated into proteins. Negative-sense RNA (-RNA) viruses have RNA that must first be transcribed into a complementary positive-sense RNA before protein production can begin The Infected Cell: There are five main effects of virus infection on the cell 1.Death (cell lysis) 2.Fusion of cells to form multinucleated cells (CPE) 3.Malignant transformation 4.No apparent morphologic or functional change. 5.Persistence inside the cell (latent infections) Infected cells frequently contain inclusion bodies, which are discrete areas containing viral proteins or viral particles.  Fusion of virus-infected Death of the cell cells A hallmark of viral infection of the cell is Cell death is probably due to the cytopathic effect (CPE) that results in inhibition of macromolecular changes in cell size, shape or multicellular synthesis, such as host cell protein fusion. and nucleic acid. Cell membrane ruptures and viruses are released. The fusion of infected cells together produces multinucleated giant cells. Fusion occurs as a result of cell It is important to note that synthesis membrane changes, which are probably of cellular proteins is inhibited but caused by the insertion of viral viral protein synthesis still proteins into the membrane. occurs. For example, poliovirus inactivates cellular mRNA to be translated into cellular proteins, but poliovirus mRNA will be translated, and then viral proteins can be synthesized  Malignant transformation Caused by infection with certain viruses, which is Infection of the cell characterized by unrestrained (uncontrolled) growth, accompanied by virus prolonged survival, and morphologic changes. production can occur without morphologic or gross functional changes. Transformation of the infected cells is resulted by: Infection with oncoviruses: some viruses have This observation oncogenes in their genetic material that when being highlights the wide inserted in host cell genome will be expressed into variations in the oncoprotein that induces malignant transformation. nature of the Examples for oncoviruses are human papilloma virus interaction between (HPV) and Epstein bar virus (EBV) and cause the virus and the cell, endometrial cancer and lymphoma, respectively. ranging from rapid destruction of the cell Complication of viral infection: sometime the high to a symbiotic rate of tissue cells destruction that is caused by the relationship in which the rapid viral replication and immune destruction will cell survives and force rapid cell division to compensate the dead cells multiplies despite the and rebuild the affected tissue, this event will increase replication of the virus. the chance of mutagenesis (mutations) which might be cancerous. Examples are hepatitis C virus (HCV) and human immune deficiency virus (HIV) that cause  Viral pathogenesis in the infected patient involves (1) Transmission of the virus and its entry into the host (2) Replication of the virus and damage to cells Viruses Pathogenesis (3) Spread of the virus to other cells and organs (4) The immune response (5) Persistence of the virus in some instances. 1- Transmission & Portals of entry  Localized or Disseminated Infections Most viral infections are either localized to the portal of entry or spread systemically through the body. The best example of the localized infection is the common cold caused by rhinoviruses, which involves only the upper respiratory tract. Influenza is localized primarily to the upper and lower respiratory tracts. Respiratory viruses have a short incubation period because they replicate directly in the mucosa of the entry site and don’t spread to other organs. Systemic infections such as poliomyelitis and measles have a long incubation period because viremia and secondary sites of replication are required  Evasion of Host Defenses (immune response) Viruses have several ways by which they evade Virulence (avoid, escape) our host defences. Strains of viruses differ greatly in Cytokine decoys: proteins that have the their ability to cause disease: ability to block host immune mediators. They are released from virus-infected cells to bind and neutralize various immune Some viruses have genes that mediators such as interleukin-1 (IL-1) and encode for: tumor necrosis factor (TNF), and thus block their ability to activate immune cells that mediate host defences against the viral infection. 1. Molecules that induce cytopathic effect 2. Malignant transformation Virokines are proteins secreted by the infected host cell and resemble (look 3. Antigenic variation so that like) cytokines, growth factors escape form immune recognition or complement regulators, they compete 4. Maintain viral latency inside a with normal host signals for their target host cell for long time. receptors. Immunomodulatory proteins that bind and destroy cytokines.  Evasion of Host Defenses Viruses have several ways by which they evade Virulence (avoid, escape) our host defences. Strains of viruses differ greatly in Cytokine decoys: proteins that have the their ability to cause disease: ability to block host immune mediators. They are released from virus-infected cells to bind and neutralize various immune Some viruses have genes that mediators (cytokines) such as interleukin-1 (IL- encode for: 1) and tumor necrosis factor (TNF), and thus block their ability to activate immune cells that mediate host defences against the 1. Molecules that induce viral infection. Cytokine cytopathic effect decoy 2. Malignant transformation 3. Antigenic variation so that cytokine cytokine escape form immune recognition 4. Maintain viral latency inside a host cell for long time.  Evasion of Host Defenses Viruses have several ways by which they evade Virulence (avoid, escape) our host defences. Virokines are proteins secreted by the Strains of viruses differ greatly in infected host cell and resemble (look their ability to cause disease: like) cytokines, growth factors or complement regulators, they compete Some viruses have with normal host signals for their target genes that receptors. encode for: Immunomodulatory proteins that bind and 1. Molecules that induce destroy cytokines. cytopathic effect Cytokine 2. Malignant transformation cytokine decoy 3. Antigenic variation so that cytokine virokines cytokine escape form immune recognition 4. Maintain viral latency inside a host cell for long time.  Evasion of Host Defenses Viruses have several ways by which they evade Virulence (avoid, escape) our host defences. Virokines are proteins secreted by the Strains of viruses differ greatly in infected host cell and resemble (look their ability to cause disease: like) cytokines, growth factors or complement regulators, they compete Some viruses have with normal host signals for their target genes that receptors. encode for: Immunomodulatory proteins that bind and 1. Molecules that induce destroy cytokines. cytopathic effect 2. Malignant transformation 3. Antigenic variation so that escape form immune recognition 4. Maintain viral latency inside a host cell for long time.  Multiple antigenic types (also known as multiple serotypes): The clinical importance of a virus having multiple serotypes is that a patient can be infected with one serotype, recover, and have antibodies that protect from infection by that serotype in the future; however, that person (the same individual) can be infected by another serotype of that virus. Serotype s The classic example of a virus with multiple serotypes is rhinovirus, which has more than 100 serotypes. This is the reason why the “common cold” caused by rhinoviruses is so common. Influenza virus also has multiple serotypes, and the severe worldwide epidemics of influenza are attributed to the emergence (appearance) of new antigenic types. HIV and hepatitis C virus have multiple serotypes, which contribute to the difficulty in obtaining a vaccine against these viruses. Note that only some viruses have multiple serotypes. Many important human pathogens (e.g., measles virus, rubella virus, varicella- zoster virus, and rabies virus) have only one serotype, and some have only a few serotypes (e.g., poliovirus has three serotypes).  Overall, the signs and symptoms of most viral diseases are caused Persistent Viral Infections by cell killing via virus-induced inhibition of macromolecular In most viral infections, the virus DOES NOT remain synthesis. in the body for a significant period after clinical recovery. Death of the virus-infected cells results in a loss of function Some viruses persists for long periods via and in the symptoms of disease, such as immune suppression 1. The action of latency genes resulted from T-cells death. 2. Location of the virus: immunologically sheltered (protected) “nature preserve” (e.g., ganglia) However, still some diseases 3. Rapid antigenic variation that are caused by virally- 4. Spread from cell to cell without an extracellular induced pathological phase, so that virus is NOT exposed to condition, such as rotavirus- antibody; and immunosuppression, as in induced diarrhea or virally- acquired immunodeficiency syndrome (AIDS). induced immunologic attack and killing of the host cells.  There are three types of persistent viral infections of clinical importance. They are distinguished primarily by whether virus is usually produced by the infected cells and by the timing of the appearance both of the virus and of the symptoms of disease. A) Chronic-Carrier B) Latent Infections C) Slow Virus Infections Infections In these infections the The term slow refers to the Refer to people who produce patient recovers from the prolonged period between virus for long periods of time and can serve as a source of initial infection and virus the initial infection and the infection for others. production stops. onset of disease (appearance Important clinical examples Subsequently, the of signs and symptoms), are chronic hepatitis, symptoms may return, which is usually measured in which occurs in hepatitis B accompanied by the years. and hepatitis C virus carriers production of virus. Clinical stages of a typical viral infection are the same as those described for a bacterial infection: Incubation period Prodromal period Specific-illness period Recovery period In some patients, the infection persists and a chronic carrier state or a latent infection occurs.  Host Defenses Host defenses against viruses fall into two major categories: Nonspecific (innate immune response), of which the most important are interferons (soluble molecules) and natural killer cells Specific (adaptive or acquired immune response), including both ADAPTIVE humoral (soluble- antibodies) and cell-mediated immunity (T cells, B cells). Interferons are an early, first-line defense, whereas ADAPTIVE (humoral immunity and cell-mediated immunity) are effective only later because it takes several days to induce the humoral and cell-mediated arms of the immune response Virology Laboratory & Treatment Strategies Laboratory Techniques Viral specimens are most commonly processed in class II biological safety cabinet. There are five approaches to the diagnosis of viral diseases by the use of clinical specimens (sample): 1. Identification of the virus in cell culture 2. Microscopic identification directly in the specimen 3. Serologic procedures to detect a rise in antibody titer or the presence of IgM. 4. Detection of viral antigens in blood or body fluids 5. Detection of viral nucleic acids in blood or the patient’s cells.  Microscopic Identification Identification of Viruses can be detected and identified by the virus in cell direct microscopic examination of culture clinical specimens such as biopsy material or skin lesions. Three different procedures can be used: The growth of viruses requires cell 1. Light microscopy can reveal cultures because viruses replicate characteristic inclusion bodies or only in living cells. multinucleated giant cells (CPE). Virus growth in cell culture 2. UV microscopy is used for fluorescent frequently produces a characteristic antibody staining of the virus in infected cytopathic effect (CPE) that can cells. provide a presumptive identification. 3. Electron microscopy detects virus particles, which can be characterized by their size and morphology.  Microscopic Identification Identification of Viruses can be detected and identified by the virus in cell direct microscopic examination of culture clinical specimens such as biopsy material or skin lesions. Three different procedures can be used: The growth of viruses requires cell cultures because viruses replicate 1. Light microscopy can reveal only in living cells. characteristic inclusion bodies or multinucleated giant cells (CPE). Virus growth in cell culture frequently produces a characteristic cytopathic effect (CPE) that can Inclusion bodies provide a presumptive identification.  Microscopic Identification Identification of Viruses can be detected and identified by the virus in cell direct microscopic examination of culture clinical specimens such as biopsy material or skin lesions. Three different procedures can be used: The growth of viruses requires cell cultures because viruses replicate 1. Light microscopy can reveal only in living cells. characteristic inclusion bodies or multinucleated giant cells (CPE). Virus growth in cell culture frequently produces a characteristic 2. UV microscopy is used for fluorescent cytopathic effect (CPE) that can antibody staining of the virus in infected provide a presumptive identification. cells.  Microscopic Identification Identification of Viruses can be detected and identified by the virus in cell direct microscopic examination of culture clinical specimens such as biopsy material or skin lesions. Three different procedures can be used: The growth of viruses requires cell cultures because viruses replicate 3. Electron microscopy detects virus only in living cells. particles, which can be characterized by their size and morphology. Virus growth in cell culture frequently produces a characteristic cytopathic effect (CPE) that can provide a presumptive identification.  A rise in the titter of antibody to the virus can be used to diagnose current infection. Detection of viral Seroconversion is the term used to describe the finding of antibody to a virus (or any nucleic acids microbe) in a patient’s serum when the patient previously had no antibody. In other Viral nucleic acids (i.e., words, the patient’s serum has converted from either the viral genome or Immunodiagnostics antibody-negative to antibody-positive. viral mRNA) can be detected in patient’s blood or tissues with IgM  indicates acute infection complementary DNA or RNA (cDNA or cRNA) as a probe. IgG  indicates chronic infection, past infection If only small amounts of or vaccination state viral nucleic acids are present in the patient, the polymerase chain reaction 4-fold Increased concentration (titer) of IgG (PCR) can be used to indicates acute infection amplify the viral nucleic acids. Detection of viral antigens Viral antigens can be detected in the patient’s blood or body fluids by various tests, but  Detection of viral nucleic acids Viral nucleic acids (i.e., either the viral genome or viral mRNA) can be detected in patient’s blood or tissues with complementary DNA or RNA (cDNA or cRNA) as a probe. If only small amounts of viral nucleic acids are present in the patient, the polymerase chain reaction (PCR) can be used to PCR amplify the viral nucleic acids. Viral vaccination A vaccine is any preparation intended to produce immunity to a disease by stimulating the production of antibodies It includes suspension of killed or attenuated microorganism (virus), products or derivatives of microorganisms. Antiviral therapies are based on: - Identification of virus directed enzymes in the infected cell -Target specific steps like cell penetration, uncoating, reverse transcription, virus assembly or maturation, etc.