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Virology (MD PhD) (Subject) / course 10 (Lesson)

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• dsDNA - stats Herpes simplex, HPV, variola carries own enzymes dsDNA viruses induce cell cycle (cause cancer)
• dsDNA - replication Rolling circle model: herpes linear genome -> circular amplification Protein primers
• ssDNA -stats slapped cheek syndrome - parvovirus no enzymes small linear genomes infects replicating cells needs splicing
• dsRNA -stats gastro& respiratory symptoms reovirus
• +ssRNA -stats polio, hep A+C ubiquitous in nature polycistronic mRNA RNA-dependent RNA polymerase
• -ssRNA -stats non-segmented: rabies, ebola segmented: Influenza, Lassa  own RNA polymerase some ambisense
• +ssRNA with DNA intermediate Retroviridae - HIV use reverse transcriptase integrate into host genome (latent)
• resistant cell no receptor - may or may not be able to support viral replication
• susceptible cell has receptor - may or may not be able to support replication
• permissive cell can replicate virus - may or may not be susceptible
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• susceptible and permissive can take up virus and replicate it
• Methods to study animal viruses Multiplication: tissue/organ culture serology: antibody-based molecular biology: DNA-RNA PCR microscopy: TEM flowcytometry: antibody based
• CPE cytopathic effect titer analysis
• MOI Multiplicity of infection numbers of infectious particles added per cell
• Hemagglutination enough viruses =  agglutination dilution to 1 HAU = button at the bottom
• function of virion proteins - protective shell - packaging of nucleic acid - delivery - recognition & binding - fusion with membrane -uncoating
• Structure -nucleocapsid = proteins+ nucleic acid - envelope = membrane hull - spikes = glycoproteins on surface
• Design -stable and efficient -repeating units -small proteins
• Metastability non-equilibrium self-assembly minimal energy
• Capsid structures - helical - icosahedral - enveloped - head & tail
• WHY SUBUNITS? - necessity: subunits are light, nucleic acid is heavy - self-assembly:  - fidelity: small protein = small gene = less errors - economy: little waste - complexity: octahedron/tetrahedron leaky
• Life Cycle 1) attachment 2) entry / penetration 3) uncoating 4) replication 5) gene expression 6) assembly / maturation 7) release
• eclipse period time from infection to appearance of mature virus
• latent period beginning of exponential phase to release
• HIV - infects cd4+ cells - cyclophilin binds to receptor heparan - gp120 binds to cd4 - coreceptor binding
• Types of penetration 1) direct penetration (polio) 2) fusion of the viral envelope (HIV) 3) endocytosis (Influenza)
• uncoating - fusion with endosome - ph changes conformation of viral proteins - envelope fuses with vesicle - or proteins form pores
• assembly - appropriate concentration of XNA and viral proteins - and at specific site
• maturation -becomes infectious - proteases involved -capsid changed
• RNA polymerase no proofreading --> error prone limited to 104 bp genome mutations often lethal, but may result in resistances
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• antigenic drift minor point mutation hemagglutinin & neuraminidase
• antigenic shift genetic reassortment two strains mix
• Viral spread localized infection spread from primary site (dissemination) presence in bloodstream (viremia) systemic infection
• acute infection sudden onset -> last short time infection > incubation period > signs/symptoms > recovery (or death) Influenza
• hidden (subclinical) infections common infection > incubation period > NO signs/symptoms > clearance of virus picornaviruses
• persistent and chronic infections acute or subclinical infection that isn't cleared virus continuously detectable hep B most DNA viruses
• latent infections start with acute, last for life no particles in latent phase occasional flare-ups herpes simplex acute infection > latent infection > acute/subclinical infection
• slowly progressive infections take many years HIV acute infection> symptoms disappear > viruses are still produced > collapse
• Virus-induced tumors DNA-dependent viruses, rarely cause cancer viruses induce transformation HBV > liver carcinoma HPV > cervix carcinoma EBV > lymphoma
• Horizontal transfer from one host to another in the same generation
• Vertical transfer mother to child
• Zoonosis naturally transmissible from vertebrate animals to humans and vice-versa

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