Viruses I Flashcards
first virus isolated?
tobacco mosaic virus
viral characteristics
obligate IC parasites
no capacity for: protein synthesis, generation of E
no cell wall/nuc
DNA/RNA, NOT both
reproduce by subunit assembly (“always the same diameter”) NOT growth/division
classification of viruses: nature of genome structure of genome envelope capsid symmetry
RNA or DNA
Single or double stranded/Segmented or non (most viruses; come in pieces: influenza, rotavirus)
present/absent
helical or cubic (icosahedral)
protein shell that encases the coral genome
capsid
polio: just genome + capsid
cell culture allows for?
before it was animals/plants
synchronized infection in cells to allow for monitoring; allowed for discovery of single-step growth curve
why the drop in viral titer?
viruses must break apart to release their genome into cells; then titer rises once machinery starts producing parts
8 steps of viral replication?
AEUERLAR
att entry uncoat early gene replication late gene assembly release
2 components of attachment?
reaction characteristics
att protein/complex
cellular receptors/co-receptors
saturable, specific, IRREV
MULTIVALENT (many different receptors/proteins) allows for high-affinity binding
types of receptors
proteins (CD4, CCR for HIV)
carbohydrates (heparin-HSV; SA-influenza)
glycolipids
host range
tropism
ability to infect a host
certain cell/tissue/organ
two ways of entry?
2 virus e.g. that can use both?
Fusion: only ENVELOPED - HIV
Receptor-mediated: BOTH
Herpes simplex, Poxviruses
receptor-mediated endocytosis entry viruses rely on what critical step?
acidification of endolysozome –> conformational change
Infervitide
prevents GP120 from folding back onto itself –> antiviral drug that prevents entry
for most viruses, what causes simultaneously with entry?
release of genome
poxviruses are unique in that they replicate where?
in cytoplasm
larger DNA viruses
IE genes
DE genes
late genes
regulatory
replication
structural proteins
smaller DNA viruses
larger DNA viruses
all but one DNA virus requires what?
uniquely dependent on host cell enzymes, polymerase
usually encode early proteins that direct cell machinery to viral genome
adeno/herpes…encode own polymerase and replication factors
host enzymes to make mRNA
POX viruses encode ALL for mRNA and DNA replication
positive strand RNA viruses have what in their DNA that negative-strands do not?
gene for polymerase
+ genome is mRNA –> polymerase production is FIRST
- genome must first be copied to + strand; polymerase is STRUCTURAL PROTEIN
retroviruses have what type of genome? significance of RT? where is RT?
+ strand
after entry, genome copied into dsDNA via RT
RT antiviral target for HIV
structural protein
why aren’t retroviruses in the + strand virus category?
because first step isn’t translation, it’s reverse transcription
hepatitis B virus unique because?
dsDNA virus, but has a reverse transcriptase! bah!
the monocistronic RNA problem:
how do viruses get around this (7)?
host cells translate 1st open reading frame in mRNA
separate promoters for each gene (rhabdo/rabies)
mRNA splicing
translate one large polyprotein that is then cleaved into indiv proteins
segment genome, each protein on different RNA (influenza/rotavirus)
frame shifting - skip bases (pseudo-knot:allows for regulating how much of each protein to make e.g skip happens 10% of the time)
IRES
most viruses use multiple methods
two viruses w/ separate promoters for each gene
rhabdo/rabies
two viruses that segment genome
influenza/rotavirus
IRES
can replace/fxn as 7’ guanosine cap
critical feature of assembly of icosahedral viruses
scaffold proteins
one viral infx that is symptomatic (most are asymptomatic)
measels
purpose of causing sx as a virus after infection?
enhances transmission
examples of vertical transmx
Rubella or CMV
occurs in utero and requires viremia
most common during primary infx
most infx are horizontal
most common mech of transmit?
#1 airways #2 GI tract GU animal vectors animal bites aerosolized needle sticks
respiratory virus transmx e.g.?
Measles
also can enter via conjunctiva
doesn’t actually cause infx in lung
humidity/temp/envelop and virus survival
low humidity up survival
lower temp enhances
non-enveloped can survive better on surfaces
tx for viral diarrhea?
hydration
not many antivirals avail
2 e.g. of fecal-oral transmx viruses that don’t cause diarrhea
enterovirus
polio
characteristics of fecal-oral transmx viruses?
large amts shed in feces
highly-resistant; survive long time in env
heat/protease/alcohol resistant
require bleach to kill
organic matter in feces protects (from bleach e.g.)
hand washing may not kill but can remove from hands
characteristics of viruses transmx by close contact? one e.g. of virus transmitted by fomites?
most are labile or shed in low amts
kissing/sex
fomites can transmit (HPV)
route of many PERSISTENT viruses
key property of viruses transmitted by insect vector?
must be able to replicate in both vertebrate host and insect
animal vector transmission chars?
emergent infections
highly lethal b/c humans aren’t natural host
transmission via direct injection
viremia required
define: productive infection permissive cell abortive infection non-permissive cell
infectious virus is produced
supports complete real cycle
non-productive; no infectious virus produced
doesn’t support replication and produces infectious virus
localized infection
virus stays at site of entry (herpes; HPV; respiratory pathogens)
CAN STILL dev systemic sx e.g. influenza, while only in lungs
disseminated infection
primary v. secondary viremia:
persistance/titer/sx/detection in BS
first time in blood: primary viremia (localized replication in epithelial cells; spreads to lymphatics; transient and low titer/doesn’t persist)
Secondary: higher titer, more sustained, target tissues now infected (liver/brain), now have sx (chance inc w/higher titer and duration of secondary viremia) can now detect virus in BS
PROCESS TAKES 10d-2wks
patterns of infx: acute v persistent
acute: acquired, defenses respond, virus cleared
persistent: acquired, defenses respond, defenses don’t clear, host infected for life/long time
2 types of persistent infx?
e.g. of each (2:5)
what virus exhibits both types?
chronic: presence of isolatable infectious virus 6 mo after initial infection (Hep B/C) –> pts are infectious at all times
latent: virus cycles btwn infectious(shed/isolatable) and when no virus can be detected (Herpes, adeno, papilloma, papova, paro); reactivated into “lytic” cycle; during latent stage, only can detect circular genome
HIV
what is the unique feature of acquisition of latent infectious viruses? one e.g.?
initial infection is asymptomatic
e.g. genital herpes
mechanisms of direct damage?
which is the major mech?
how does this occur (3)?
host shutoff (of gene expr; viruses cherry-pick genes) inhibition of host translation
alter phosphorylation of initiation proteins
proteolytic cleavage of init factors
digestion of mRNA
inhibition of host gene expression (3)
block RNA pol (pol II)
interfere w/splicing of mRNA
interfere w/transport of mRNA to cytoplasm
the above will kill the cell
interfering w/cell cycle (3)
shutoff halts cell cycle
DNA viruses push S phase than stops it before replication –> incr expression of proteins used in replication (cells make for viruses to use)
common to cancer-causing viruses
def: infection results in changes in cell shape
cytopathic effect
rounding/detachment
development of inclusion bodies (e.g. Negri body: rabies, HCMV, RSV)
syncycium formation plays what role in infection?
allows for viral spread in presence of neutralizing antibodies
primary v immortilized v transformed cells
limited lifespan then enter senescence
mutant primary cells that overcome senescence; grow continuously; do not cause tumors in animals
mutant immortalized cells that lost anchorage independence and form tumors in animals
acute (one e.g.) v. chronic (one e.g.) cancer viruses
carry genes that drive the transformation process (and thus have short incubation period); polyclonal tumors; multiple tumors can arise at the same time; HHV8 Kaposi’s
do not carry directly transforming oncogene but makes cells more likely to acquire new mutations bc of frequent division; immortalize cells; require additional mutations to cause cancer; long incubation; monoclonal tumors; HPV cervical cancer
viruses and their assoc cancer: HTLV HHV8 EBV HepC/B Merkel HCMV
adult T-cell leukemia Kaposi's, lymphoma, Castlmans cervical, anogenital, skin, H/N lymphoma, nasopharyngeal, GI hepatocellular merkel cell gliomas, GI
risk factors for infection
age
hormones (pregnancy e.g. HepE)
nutrition (immune fxn)
fever
infection chain of events
epithelial cells –> TLR’s recognize –> IFN-1 (via nFkB) –> adjacent cells –> rig-1/MDA5 recognize viral RNA’s and induce IFN –> cytokines attract NP’s –> PMNs infiltrate and cytokine release to attract T-cells –> APCs pick up and tax to nodes –> T/B cells activated –> antibodies
single most important defense mech we have?
interferon
e.g. most infectious of common cold just before you have sx
antimicrobial peptides e.g.
made by host cells
alpha/beta cathelecidines
pores in bact
bind to viruses that block attachmt; can also disrupt envelope
interferon!
3 critical unregulated genes
Type I a/B
binds to cell surface and induces 300 different genes
spp specific, not virus specific (e.g. mouse IF doesn’t do squat in humans)
IFN mechanisms (3)
PKR: phosphorylates eIF2a –> cells can’t initiate any protein synth
Ribonuclease L: nuclease specifically digests mRNA (both cell and viral)
MXA: binds influenza virus polymerase and prevents fxn
these are made and then SIT THERE in an inactive conformation
signals to activate the 3 death proteins:
PKR via binding to dsRNA
RNAse L via ds RNA and 2’5’oligoadenylate (2asynthase activated by dsRNA)
(dsRNA present at high levels in virus infected cells)
viruses fight interferon with?
interferon!
- secrete soluble IF receptor decoy (binds to IF in system)
- block phosphorylation and thus signal transduction
- proteolytically digest signal messengers in pathway to shut down IF response
- sequestering proteins that bind messengers
- turn on SOX proteins that naturally damper IF response
how does antibody block viruses?
can bind and neutralize via blocking attachment or uncoating
ab binding to infected cell and suppress gene expression
opsonization–>phagocytosis
Fc mediated complement activation
antibody enhancement
e.g.?
non-neutralizing abs bind to virus –> Fc exposed –> cells w/Fc receptors take up virus that would otherwise be non-permissive cell –> dengue hemorrhagic fever
MP’s secrete tons of TNF-a –> vascular leakage –> hemorrhage
a concern for HIV-related vaccination
interesting fact about vaccines?
don’t prevent infection; just sx (except HPV)
viral immune evasion
cytokine interference via blockage of antiviral proteins activated by IF, decoy receptors, immunosupprx cytokine analog encoded by virus, produce peptides that cannot be digested to then be presented (EBV)
most common way to damper immune system?
interference w antigen presentation: block transport into ER, loading onto MHC, trap MHC in ER, downreg expression of MHC proteins (reduce transcription/induce endocytosis of cell surface proteins)
other viral mechanisms to interfere w immune sys
virus has Fc receptor
encode proteins that bind complement
down reg of co-stim molecules
induce apoptosis of T’s (HIV gp120 can kill T’s)
immune exhaustion
escape variants (mutates so sys can’t see it –> HIV/HepB –> causes viral titer to keep going up and down bc mutant variants escape)
which virus has a rapid mutation rate?
HIV
e.g. of type 1 hypersensitivity response
respiratory viral infections can exacerbate asthma
ADCC is seen in what?
type II
Fc portions of antibody binds to Fc receptors on NK/MP/PMNs
leading cause of infectious blindness in the US?
Herpes
herpes simplex keratits in an example of what type hypersesitivity?
type IV
Name the virus: enveloped/icosahedral naked/helical naked/isosahedral enceloped/helical
herpes
tobacco mosaic
adenovirus
measles
direct fusion entry 2 e.g.?
receptor-mediated endocytosis 2 e.g.?
both routes 1 e.g.?
herpes/HIV (fusion protein –> pore)
influenza/rotavirus (phagolysosomes –> acidification and release)
herpes simplex
requires lysosomal proteases to cleave capsid to allow for passage into cell?
rotavirus
the tactic of “ribosomal frame shifting” is used to make which key viral protein?
reverse transcriptase
Picornaviruses solve the monocistronic mRNA problem by which strategy?
IRES
what’s funky about polio and coxackie virus and their portal of entry?
enter via GI but don’t cause GI sx
name two viruses that can enter via inhalation of urine/feces?
hantavirus and lassa fever
