Pathology and Pathogenesis of Viral Infections PDF

MVI: Molecular Virology and Immunology Course Coordinator: Dr George Krashias * : [email protected] ( : 22392648 19-11-2024 Department of Molecular Virology Path...

MVI: Molecular Virology and Immunology Course Coordinator: Dr George Krashias * : [email protected] ( : 22392648 19-11-2024 Department of Molecular Virology Pathogenesis of viral infections Outline Definition of viral pathogenesis General patterns of viral infections Infection vs disease Sign and symptoms characterizing viral diseases Factors that determine the development of disease/Host vs viral factors Viral evasion strategies Study of viral pathogenesis Department of Molecular Virology Viral pathogenesis Viral pathogenesis is the process by which a viral infection leads to disease. Viral pathogenesis is an abnormal situation of no value to the virus. The majority of viral infections are subclinical. The consequences of viral infections depend on the interplay between a number of viral and host factors. Department of Molecular Virology General patterns of viral infection Acute Influenza HBV Chronic Latent EBV Slow HIV Time Department of Molecular Virology Equilibrium and non-equilibrium states in pathogenesis Acute infection Chronic infection Non-equilibrium state Equilibrium state Host response and virus Viral and host process are infection change balancing each other continuously Outcomes?? Outcomes?? Department of Molecular Virology Infection vs Disease Infection is the invasion of an organism’s body tissues by a microbial agent, its replication, and the reaction of host tissues to the invading microorganisms Disease is a harmful pathological consequence of infection that in most cases is associated with specific symptoms Not all viruses cause diseases but all viruses must establish an infection to have the potential to cause diseases Nonspecific symptoms vs specific signs and symptoms of diseases Department of Molecular Virology Common signs and symptoms of viral infection Classic signs and symptoms: Occur in advance of more virus-specific signs and symptoms Associated with activation of the innate immune response IFN-α/β IL-1β Department of Molecular Virology Gastrointestinal infections Rotaviruses and noroviruses are two of the most significant agents that can infect the gastrointestinal tract Rotaviruses pass through the stomach following ingestion and infect the cells at the tips of the villi of the epithelium lining the small intestine Section from the ileum of a piglet Section from the ileum of a 72 hrs post-infection with non-infected piglet rotavirus Intestinal epithelium is responsible for absorption of nutrients from the gut contents The osmotic balance across the epithelium is lost and there is an outflow of water and electrolytes from the body into the lumen of the gut Department of Molecular Virology Respiratory infections Specific signs and symptoms: coughing and sneezing Sneezing: a reflex response of irritation and build-up of fluid in the nasal passages Coughing: results from build-up of mucus when viruses infect lower in the respiratory tract Severity of respiratory signs and symptoms in these infections broadly relates to how deep into the respiratory tract infection penetrates Rhinovirus vs influenza A virus Department of Molecular Virology Infections of the liver Several viruses can infect the liver and cause hepatitis Inflammatory condition of the liver Appearance of jaundice Why?? Example: HAV Transmission route: fecal-oral route Normally cleared Also cause gastrointestinal symptoms Does not appear to kill hepatocytes Damage to the liver is due to CD8+ T cell responses Department of Molecular Virology Systemic spread Some viruses are capable of causing disease at a site away from the primary site of infection Examples: Measles virus Rash: smooth discoloration of the skin Department of Molecular Virology What determines whether a virus can spread away from its site of initial infection? Being able to infect cells that move from the initial site of infection How the virus exits the cells it originally infects Department of Molecular Virology What determines the outcome of a viral infection? Hosts differ significantly in genetic susceptibility to infection CCR5 mutations and resistance to HIV-1 infection HSV-1 and HSE Autosomal dominant mutations within TLR3 drives the development of HSE Individual status CMV infection in (a) an immunocompetent individual (b) an immunocompromised individual (c) a pregnant women Department of Molecular Virology Virulence The relative capacity of a virus to cause disease Determines the relationship between infection and disease High virulent viruses vs low virulent viruses Virulence comes in many forms: Induction rapid death Induction of tumors Induction of organ failure Comparing virulence of viruses Virulence is a property used to compare the disease-causing capacity of related viruses, such as different strains of the same virus Department of Molecular Virology Viruses: evasion of the immune response to cause disease Interference with the MHC class I presentation pathway Department of Molecular Virology  Viruses: evasion of the immune response to cause disease Interference with the MHC class II presentation pathway Interfere with the HIV-1 Tat competes with MHC class II expression of Down-regulating transactivator and represses the expression MHC II antigens their transcription of genes encoding for MHC class II antigens Interfere with the HIV-1 Nef promotes the expression of immature rather than loading of peptides mature MHC II on the surface of infected cells onto MHC II antigens Interfere with the Disrupting the Downergulation of costimulatory molecules. presentation to interaction between HHV8 downregulates B7.2 naïve CD4+ T cells MHC II and TCR Department of Molecular Virology Viruses: evasion of the immune response to cause disease Interference with the function of NK cells Missing self hypothesis NK inhibitory and activating receptors HLA (human leukocyte antigen) system is also known as the human version of the MHC found in many animals NK inhibitory receptors recognize HLA-C and HLA-E in particular HLA-A and HLA-B present virus- derived antigenic peptides to CTL Department of Molecular Virology Viruses: evasion of the immune response to cause disease HIV-1 infects CD4+ T cells HIV-1 EBV Targeting Latency immune cells Targeting Inhibit cytokines of apoptosis EBV and HCMV the host HPV E6 encode IL-10 homologues Department of Molecular Virology The study of viral pathogenesis Several tools utilized in studying viral pathogenesis Epidemiology An essential tool for pathogenesis research for defining patterns of diseases and the mode of transmission between hosts 1918 United States Department of Molecular Virology The study of viral pathogenesis Animal models 1st Animal model: Passage-based Ebola adapted to infect Studies a human adaptation of the human guinea pigs and mice virus in an animal virus to grow in an experimental animal Not all human viruses can replicate in animals Transgenic expression of the poliovirus HIV-1 infection of humanized mice or measles virus receptors in mice Creation of humanized mice Engineering of the host to accommodate part of the human infection Targeted modification of viruses to allow replication in a model host SHIV 2nd Animal model: Studies an animal virus that is related to a human virus in its animal host Department of Molecular Virology The study of viral pathogenesis Cell culture An essential tool for the study of viral replication and tropism Several caveats Conditions do not fully resemble conditions in vivo Absence of cellular immune responses Often optimized for synchronized infection of all cells Composed of cell that are transformed or continuous cell lines Department of Molecular Virology  Questions? Department of Molecular Virology