lect 6: animal viruses

Introduction

  • 4 diff types of infection:

    • 1. lysis - ~lytic, lyse cell to release virus

    • 2. persistent - ~M13, don’t lyse the cell but alter its metabolism, virus secreted from host cell

    • 3. transformation - cell goes from normal to tumor

      • neoplastic transformation - cell goes from normal to cancerous tumor cell

    • 4. latency - NOT lysogeny but looks similar, virus infects but doesn’t do anything big, stays in hibernation state until conditions improve then goes thru lysis

      • some can integrate itno genome

      • latency developed as coincidental event that involves the virus infecting a cell diff from its usual target (meaning in diff environ)

  • enveloped vs nonenveloped viruses

    • DNA viruses: ds and ss in nonenveloped, mostly ds in enveloped

    • RNA: ds and ss in nonenveloped, only ss in enveloped

  • host affinity is dept on the ability of the virus to dock to the cell

    • if no specific P or molec present in potential host cell, virus can’t bind and won’t infect


Piconaviruses: Poliovirus

  • phylogenetics:

    • family: piconaviridae

    • genera includes: polio (infects primates), cardiovirus (ex. EMCV, infects mice), and aphthovirus (ex. foot and mouth, infects even toed hoof animals)

  • structure: icosahedral capsid (w/o envelope) surrounding + stranded ssRNA genome

    • capside made of 60 protomers, each have 3 surface P (VP1, 2, 3) and most have additional internal P (VP4)

  • genome is +ssRNA so genome gets transl immediately to make P and has 1x ORF

  • UTR at both ends form secondary struct that’re essential for genome function, facilitate transl, and protect from transl

    • mRNA has no 5’ cap but has VPg (P) that plays same role (protect against degradation)

    • polyA tail is present at 3’ end and is heterogeneous in length

  • life cycle:

    • genome → make poly P → cleave → proteases, RNA replicases, structural P coat

    • genome → -strand → new +strands → P, packaged

      • both pathways happen at once - need RNA replicase to make -strand and more +strands

    • assemble new virions

    • then lyse infected host cell to release progeny virions

  • viruses usually multiply in GI tract but can multiply in other tissues

  • infections are usually asymptomatic

    • clinical manifestations include common cold, mild meningitis, encephalitis, myelitis, myocarditis and conjunctivitis

    • don’t need to memorize specifics

  • transmission primarily via oral/fecal route

  • incidence of infection inc with age of infected subject

    • meaning that kids infected usually aren’t affected but teenagers, young adults, and older are

    • inc polio when sanitation started becoming commonplace bc kids weren’t getting infected with polio so when ppl were exposed when they were older, they were affected more seriously


Rhabdoviruses

  • phylogenetics:

    • family: rhabdoviridae

    • genera includes: lyssavirus (rabies), vesiculovirus (VSV)

  • structure: enveloped, bullet/cone shapes

    • nucleocapsid is a helical ribonucleoP complex, made up of ssRNA, nucleoP, RNA dept RNA polymerase, and phosphoP

    • the lipid envelope contains envelope P that interact with the ribonucleoP complex via the matrix P

  • genome: -ssRNA, linear, at least 5 ORFS

    • genome is template for replicase to make +ssRNA → -ssRNA for progeny

  • noninfectious - isolated RNA don’t do anything bc need RNA dept RNA polymerase in virion to transc +strand

  • subgenomic RNA pieces used to make P (direct transl of viral P)

    • not made from long mRNA cut into pieces

  • humans aren’t normal host, usually seen in bats, wolves, dogs, other small carnivores

    • we’re an evolutionary dead end bc we don’t bite each other (spreads virus)

    • virus adapts host behavior to inc viral pop and spread (salivating, avoid water, bite everything)


Papilloma & Polyoma Viruses

  • used to be classified as same thing

  • small, circular, dsDNA genomes

  • nonenveloped

  • replicate and transc in host cell’s nucleus → uses all host cell machinery

    • makes them model orgs for ID euk DNA replication components

  • can integrate into host genome

  • have 1x oor → simple sys

  • genome divided into early and late regions

  • can cause cancer in some hosts and specific conditions


Polyoma Viruses : SV40

  • phylogenetics:

    • family: polyomaviridae

    • genera includes: mouse / human polyoma, SV40

  • all can cause cancer / tumor growth

  • transc goes from early → late region

  • bidirectional transc, transc from opposite strands

  • DNA → RNA transc → alt splicing results in all necessary P

    • gene transcripts reg by alt splicing

  • early regions: P involved in DNA replication and neoplastic transformation

    • includes large and small T antigen - alt splicing results in conditional pdction of large vs small

    • large T antigen drives tumor / cancerous growth while little T can mod replication

  • late regions: virus particle structure P

  • usually infects primates (not transform them) but when infect rodents, it does transform rodent cells

    • mouse polyoma virus can cause tumors in nonmouse rodents

    • can neoplastically transform mouse cells but only causes tumors in neonatal and immunocompromised ones

  • infection process:

    • 1. infect permissive host → nonpermissive infection can happen but less likely

    • 2. viral DNA integrated into host genome

      • nonspecific location of integration for both host and viral genome

      • usually result in fucked up viral genome or host genome, which can render either one nonfunctional

    • 3. pdce large T antigen

    • 4. transc tumor virus mRNA

    • 5. transl

    • 6. cell transform into tumor


Papilloma Virus

  • phylogenetics:

    • family: papillomaviridae

    • genera includes: human / bovine papilloma

  • cause benign or malignant tumors as well as warts

  • some can cause cancer

  • early and late genes transc from same DNA strands and both are reg by alt splicing

  • early genes: involved in DNA replication, viral transc, host cell reg, and neoplastic transformation (E1 - 7)

    • few are oncogenetic and inhibit cell’s tumor supressor genes → promote uncontrolled growth

  • late genes: virus particle structural P (E1 - 2)

  • all restricted to infecting keratinocytes → skin and mucosal epithelia

  • transmitted via direct contact

  • highly species specific


Herpesviruses

  • phylogenetics:

    • family: herpesviridae

    • genera includes: simplex viruses (human herpesvirus 1/2), varicellovirus (chicken pox, human herpesvirus 3), epstein-barr (human herpesvirus 4), cytomegalovins (human herpesvirus 5)

  • genome: large, circular, dsDNA

    • linear in virion, circularize in host cell

    • divided into immediate early, delayed early, and late regions

  • replic and transc in host cell nucleus

  • capable of latency

  • can infect keratinocytes, epithelial, and nerve cells

    • when infect nerve cells, goes thru latency and stays dormany until exp stress, then cleaves itself from the genome

      • when in latency, max replication capacity isn’t reached or required - only few copies made and v few viral genes expr

    • virus secreted to epithelial cells

  • can cause cancers in some hosts and under certain conditions

  • undergoes rolling circle replication

  • packaging ~lambda but use diff seq

  • 3 big genera but 13 genera overall that fit large num of viruses

  • v host speciifc

    • most are confined to mucosal epithelial or lymphocytes but large range possible

    • can be separated into virulent and latent types

  • requires direct contact for transmission


Pox Viruses

  • v complex mem, large

  • have genome, viral E, structural proteins

    • almost like intmd to cell

  • have lot of ORFs and read both strands

  • variable regions conserved btwn species

  • includes E that mod nucleotides, their metabolism, ATPase, and so on

  • dsDNA but weird

    • like ssDNA circle that collapsed on itself

    • dsDNA with sealed ends ~ chr

  • process:

    • 1. attach to GAGs on outside of host cell

    • 2. outermem fuses with cell’s plasma mem

    • 3. insert inner mem (+ all contents) into host cell

    • 4. early transc + DNA replication by viral polymerase - all happen in cytoplasm

    • 5. inner mem gone by now and genome is free in cytoplasm, intmd genes expr

    • 6. late genes expr → structural P made

    • 7. progeny assembly

    • 8. cell lysis and progeny release