Introduction to Virology PDF

Introduction: Viral Effect on Host Cell, Mechanisms of Viral Pathogenesis, Role of Viruses in Disease Professor: Dr. Jordan M. Callueng Trans by: Alicog, Flores, E. Definition of Terms For the Non-Medt...

Introduction: Viral Effect on Host Cell, Mechanisms of Viral Pathogenesis, Role of Viruses in Disease Professor: Dr. Jordan M. Callueng Trans by: Alicog, Flores, E. Definition of Terms For the Non-Medtechs Tips on Viral Classification Although comprehensive, memorizing the tables provided in the lecture may be overwhelming to some. A helpful approach during Viruses Poison/toxin; our undergrad (and until now!) would be through diagrams. Obligate intracellular parasites; At a minimum: have a nucleic acid genome with Legends are as follows: a protein coat. N: Naked (i.e., not covered with an envelope) E: Enveloped I: Icosahedral Viroids Small, circular, single-stranded RNA infectious H: Helical pathogens of plants that do not have a protein (+): Positive-sense single-stranded RNA coat. (-): Negative-sense single-stranded RNA Virusoids Small, circular-RNA, infectious pathogens I highly recommend knowing this by heart, especially the (Defective generalizations. Try writing it down by yourself. Hope this helps! Depend on viruses to provide the proteins for Virus) their replication and protein coat Prions Misfolded proteins Spread from one cell to another, causing the same protein molecules to misfold in the new cell Generalizations: DNA viruses 1.​ ALL DNA viruses are icosahedral and replicate in the nucleus, except POXVIRIDAE (complex; in cytoplasm). VIRAL STRUCTURE 2.​ Sizes: ○​ Largest: POXVIRIDAE Virion Complete virus particle ○​ Smallest: PARVOVIRIDAE Genome Can consist of single- or double-stranded RNA or DNA; Can comprise >1 genome segments. Capsid protein shell, or coat, that encloses the nucleic acid genome Nucleocapsid Protein–nucleic acid complex representing the packaged form of the viral genome Envelope Lipid-containing membrane that surrounds some virus particles Peplomers glycoproteins on the surface of the envelope Generalizations: RNA viruses 1.​ ALL naked RNA viruses are icosahedral. These include “PCR” (Picorna, Calici, Reo). 2.​ ALL (-) ssRNA are enveloped and helical. 3.​ Vector-borne viruses include: TBF (Toga, Bunya, Flavi) 4.​ ALL replicate in the cytoplasm, except: Orthomyxo, Retro (ReTrO → uses REverse TRanscriptase) 5.​ Sizes: ○​ Largest: PARAMYXOviridae ○​ Smallest: PICORNAviridae PAGE 1 BATCH TALAGHAY  Major Families of Human Pathogenic Viruses DNA Viruses RNA Viruses Portal of Entry to Human Host PAGE 2 BATCH TALAGHAY | Alicog, Flores, E.,  Viral Replication & The Growth Cycle Viral replication is a localized process, occurring within morphologically discrete cytoplasmic or nuclear structures variously termed viral inclusions (or inclusion bodies), virosomes, viral factories, or viroplasms. INCLUSION BODIES PRODUCED IN VIRAL INFECTIONS Intracytoplasmic inclusion bodies Negri bodies Rabies virus Molluscum bodies Molluscum contagiosum virus Guarineri bodies Vaccinia virus 1 | Binding/Attachment Bollinger bodies Fowl pox virus Virus binds to specific receptors on the cell surface. Perinuclear cytoplasmic Reovirus acidophilic bodies Intranuclear inclusion bodies Owl’s eye inclusion bodies Cytomegalovirus (CMV) Cowdry type A HSV, Measles Intranuclear basophilic Adenovirus Acidophilic Papovavirus Negri bodies (left) & Owl’s eye inclusion bodies (right) 📝 Steps in Viral Replication 1.​ Binding 2.​ Cellular Entry 3.​ Uncoating 4.​ Transport to the site of replication 5.​ Transcription of mRNA 6.​ Translation of viral proteins 7.​ Replication of input genome (nucleic acid amplification) 8.​ Assembly of progeny viral particles 9.​ Egress from the cell PAGE 3 BATCH TALAGHAY | Alicog, Flores, E.,  2 | Cellular Entry/Penetration 8 | Assembly Virus then enters by one of the pathways: a)​ Endocytosis followed by fusion with the endosome membrane b)​ Fusion of the envelope with the surface plasma 9 | Release membrane 3 | Uncoating/ Disassembly ​ Occurs concomitantly with or shortly after penetration ​ Physical separation of the viral nucleic acid from the outer structural components of the virion so that it can function. ​ Via budding by enveloped viruses (directly from the ​ The genome may be released as free nucleic acid cell membrane as in the case of HIV) (picornaviruses) or as a nucleocapsid (reoviruses). ​ Into a secretory pathway (Hepatitis C virus) ​ The infectivity of the parental virus is lost at the ​ Cell lysis by non-enveloped viruses uncoating stage → “eclipse period” Viral Effects on Host Cell Hallmark of viral infection of the cell: Cytopathic effect (CPE) ​ This change in the appearance of the infected cell usually begins with a rounding and darkening of the cell and culminates in either lysis (disintegration) or giant cell formation. ​ Detection of virus in a clinical specimen frequently is based on the appearance of CPE in cell culture. ​ Basis for the plaque assay, an important method for quantifying the amount of virus in a sample. 📝 In general: RNA viruses induce apoptosis of host cells. DNA viruses encode proteins that block apoptosis. 4-7 | Expression of Viral Genomes & Synthesis of Viral Components Apoptotic cell death is characterized by: ​ Cell shrinkage ​ Membrane blebbing – ​ Condensation of nuclear chromatin ​ Activation of an endogenous endonuclease ○​ Cleaves cellular DNA into oligonucleosome-length DNA fragments PAGE 4 BATCH TALAGHAY | Alicog, Flores, E.,  Virus-Host Interactions TROPISM (n). capability of a virus to infect a distinct group of cells in the host ​ Pathogenesis ○​ Process whereby a virus interacts with its Determinants: host in a discrete series of stages to produce 1.​ Availability of virus receptors on the surface of a disease. host cell ​ Virulence ○​ Cells not susceptible for poliovirus replication ○​ Capacity of a virus to produce disease in a could be made susceptible by recombinant susceptible host expression of the poliovirus receptor. 2.​ Post-attachment steps in viral replication, such as the regulation of viral gene expression ○​ Some viruses contain genetic elements, termed enhancers, which act to stimulate transcription of viral genes. ○​ The promoter-enhancer region of John Cunningham (JC) polyomavirus is active in cultured human glial cells but not in HeLa cervical epithelial cells. 3.​ Route of entry and pathway of spread ○​ Encephalitis viruses transmitted to humans by insect bites undergo local primary replication and then spread to the CNS by hematogenous and neural routes. ○​ After oral inoculation, VEE virus is incapable of primary replication and spread to CNS. 4.​ Age, nutritional status, immune responsiveness, and certain genetic polymorphisms that affect susceptibility to viral infection ○​ Vitamin A deficiency → enhanced 📝 Viral Pathogenesis susceptibility to measles virus infection 1.​ Viral entry into the host 2.​ Primary viral replication Host Response to Infection 3.​ Viral spread 4.​ Cellular injury 5.​ Host immune response INNATE IMMUNITY 6.​ Viral clearance or establishment of persistent infection 7.​ Viral shedding The innate antiviral response is a local, transient, antigen-independent, perimeter defense strategically focused at the site of virus incursion into an organ or tissue. Viral Spread and Cell Tropism ​ Viral PAMPs in the form of single-stranded (ss)RNA, dsRNA, RNA 5′ triphosphate, and DNA evoke the innate immune response through groups of PRRs. ​ Nucleic acid binding by PRRs activates signaling pathways leading to the production and extracellular release of IFN-α, IFN-β, and proinflammatory cytokines such as IL-1β and IL-18. ○​ IFN-α and IFN-β engage the cell surface IFN-α/β receptor and thereby mediate expression of hundreds of gene products that corporately suppress viral replication and establish an intracellular antiviral state in neighboring uninfected cells. PAGE 5 BATCH TALAGHAY | Alicog, Flores, E., Well-described IFN-inducible gene products, both of which are ADAPTIVE IMMUNITY activated by dsRNA, include: The adaptive immune response confers systemic and ​ Latent enzymes dsRNA-dependent protein kinase enduring pathogen-selective immunity through expansion and (PKR) functional differentiation of viral antigen–specific T and B ○​ Inhibits the initiation of protein synthesis lymphocytes. through phosphorylation of translation initiation factor eIF2α Roles of Different T-cell Subtypes ​ 2′,5′-oligoadenylate synthetase (OAS) T lymphocytes are centrally positioned in the scheme of adaptive immunity. ○​ 2′,5′-oligoandenylates generated by OAS ⭐ bind and activate endoribonuclease RNase CD8+ CTL Primary cell type involved in the resolution of acute L, which degrades viral mRNA. viral infection Function: Induces lethal pro-apoptotic signaling in In addition to mediating an intracellular antiviral state, IFN-α/β virus-infected cells on recognition of endogenously also stimulates the antigen-independent destruction of produced viral protein fragments presented by cell virus-infected cells by a specialized population of lymphocytes surface MHC class I molecules known as NK cells. CD4+ T cells Recognize MHC class II associated viral oligopeptides processed from exogenously acquired proteins; Also demonstrate cytotoxicity against viral antigen-presenting cells. Function: Orchestrate & balance cell-mediated (CTL) and humoral (B cell) responses to infection. Th1 and Th2 Development of cell-mediated and humoral responses, respectively, to viral infection Tfh Promote differentiation of antigen-specific memory B cells and plasma cells within germinal centers REFERENCES Doc Jordan Callueng’s PPT. (January 2025). Loscalzo, Joseph. (2022). Harrison's principles of internal medicine vol. 2, 21st international ed. (21). New York:McGraw Hill. Riedel, Stefan, Morse, Stephen A, Mietzner, Timothy A, Miller, Steve. (2019). Jawetz, Melnick & Adelberg's Medical Microbiology (28th). New York: McGraw-Hill Education. PAGE 6 BATCH TALAGHAY | Alicog, Flores, E.,