Micro 3 Flashcards
what’s tegument and which virus has it?
protein b/w capsid and envelope –> virion stabilization, transpxn factors; HSV
general characteristics of HSV
cause lytic and latent infxn, cause syncytia and inclusion bodies, initiala binding to heparan sulfate, painful lesions
dzs b/w HSV 1 vs 2
above the waist, herpes labialis, gingivostomatitis, temporal lobe encephalitis, keratoconjunctivitis, herpetic whitlow, herpes gladitorium vs herpes genitalis, meningitis (6-60y), neonatal encephalitis
neurotropic spread vs latent infxn vs recurrent dz of HSV
retrograde to sensory ganglia vs maintained as episomes, regulation of viral transcpxn by latency-associated transcripts, CMI vs replication = reactivated, anterograde viral spread along nerve to peripheral tissue, manifests at site of primary infxn
diff b/w primary and recurrent dz for HSV depends on?
prodrome (length, systemic sxs) and local sxs (length, severity)
why are there lesions for HSV?
direct tissue dmg by lytic infxn AND host immune response/CMI (CD8, CD4 Th1)
why does congenital HSV occur?
neonate has immature immune system –> lack ab –> screen mom carefully
how to dx HSV?
Tzank, pap smear, cowdry type A body, syncytia, ophthalmic staining solutions, PCR
2 phases of dissemination and viremia for VZV
1st phase = resp to liver, spleen, organs; 2nd phase = organs to skin
VZV = benign and self limiting dz but what complications occur for immunocompetent vs compromised children?
bacterial superinfxn vs protracted varicella, multiorgan involvement, hemorrhagic varicella
explain immune response for VZV
viral cytopathicity AND host immune response give rash; ab limits dissemination but little role b/c cell to cell spread by syncytia –> CD8 and IFNy = critical for controlling virus; but high CD8 –> inc cytok prod –> interstitial PNA in adults
how to dx VZV?
by sxs or confirmed by CPE (Cowdry type A intranuclear inclusion bodies, syncytia)
vaccines for VZV
generally live attenuated vax to make ab; zostavax = live atten vax and shingrix = recombinant protein vax for adults >50y
where is CMV found in?
blood, tissue, most body fluids
CMV transmission
congenital, sex, oral, vertical (replicating in cervix), organ transplant, blood transfusion
CMV sxs
mostly asx, can become carriers
how to dx CMV?
cytomegalic cells (enlarged cells w/ intranuclear and intracytoplasmic inclusion bodies; detected in circ)
HHV 6/7 transmission
saliva (initial replication in salivary gland)
when is HHV 6/7 reactivated?
immunosuppressed and AIDs pts
what causes HHV 6/7 rash? diff b/w HHV 6 and 7?
anti viral DTH. 7 = milder dz
dissemination of parvovirus
initial site = resp tract –> disseminates to bone marrow then other tissues
can B19 infect other animals?
no, it’s an only human pathogen
parvovirus B19 biphasic dz
phase 1/febrile stage: infectious stage (7-10d), lytic infxn, non-specific flu like sxs
phase 2/symptomatic stage: noninfectious stage (1-2wk in children, mo in adult), immune mediated rash and arthralgia, slapped cheek rash
child vs adult dz for parvo B19
more arthralgia than rash in adults b/c higher ab titers
receptor of parvo B19. primary virulence factor?
P ag (globoside) on erythroid precursor cells, integrin = coreceptor on erythroid precursors but not on mature RBCs. lytic infxn on erythroid precursor cells
what happens if pregnant women get infected w/ parvo B19?
hydrops fetalis; no evidence parvo B19 causes congenital defects; no inc risk for seropositive pregnant women
what kind of immunity fights parvo B19?
strong ab response –> immune mediated rash and arthralgia; little role for CMI b/c it targets RBCs which don’t express MHC
how to dx parvo B19?
clinical sxs like the rash, ELISA in pregnant women
virulence factors of AdV
lytic infxn, persistence in lymphoid tissue, no envelope
receptor vs tropism for AdV
Coxsackie adenovirus receptor vs muco/epith cells, lymphoid cells, target cell depends on fiber and penton proteins (fibers binds to CAR, penton binds to coreceptor); incubation = 4-9d and infectious for wks when shedding in nasal secretions and stools
dz caused by Ad3/7 vs Ad4/7 vs AdV5 vs 40/41/42
pharyngoconjuctival fever (pharyngitis + conjunctivitis), from unchlorinated pools vs acute resp dz in mil recruits, atypical PNA vs pharyngitis vs gastroenteritis
at risk ppl for AdV
immunocompromised, children <14yo, ppl in crowded areas
how to dx AdV?
sx and elim of other pathogens, basophilic intranuclear inclusion bodies on cx
how to prevent vs tx AdV?
ab but serotype specific, hygiene, live Ad4/7 vax for mil recruits vs supportive
AdV as biotherapeutic
deletion of genes –> vector replication-incompetent, gene therapy –> deliver fxnal copy of mutated genes, vax vector –> give gene encoding ag
epidemiology of polyomavirus
primary infxn asx, CD8 control –> latent infxn in kidneys, reactivation in immunocompromised d/t lost CMI
how to tx polyomavirus?
supportive, inc immunocompetence
at risk ppl for reactivation of polyomavirus
HIV, transplant, immunosuppressed pts
JC vs BK dz of polyomaviruses
latency in kid, cross blood brain barrier –> infect oligodendrocytes and astrocytes –> PML –> demyelination –> progressive sxs like clumsiness, weakness, change in vision & speech, fatal 1-4mo post dx vs BKV-associated nephropathy in kidney transplants –> kid dmg d/t lost CD8 response
how does poxvirus replicate entirely in cyto?
brings DNA dep RNA pol, encodes DNA dep DNA pol, encodes viral thymidine kinase
human vs zoonotic pathogens of poxvirus
smallpox/variola, molluscum vs vaccinia virus, cowpox, monkeypox, orf virus
smallpox dz
viremic and lymphatic spread –> rash erupts over entire body at same time
how did Edward Jenner make smallpox vax? impact?
thought milkmaids don’t have smallpox due to their
infection with cowpox –> made vaccinia virus vax –> CMI. 1970: global vaccination program; key to eradication = human only pathogen
how to dx molluscum?
lesion appearance, molluscum body (eosinophilic intracytoplasmic inclusion body in infected keratinocyte)
can natural infx of smallpox give good immunity?
yes can give life long immunity but poxvirus can encode proteins w/ immunosuppressive activity; common ag determinants b/w fam –> cross reactive immunity
how to dx poxvirus infxn?
lesions at same stage (chickenpox at diff stages), pt hx, PCR of lesion fluid
how to tx vs prevent poxvirus?
quarantine or modified behavior, target VTK vs vaccinia virus live attenuated vax, OSHA recs
can poxviruses be used as viral vectors?
yes b/c well-characterized genomes –> modified vaccinia ankara, fowlpox and canarypox
general zoonotic poxvirus dz
animal pox viruses; single nodular lesion –> cluster of vesicular lesions
monkeypox vs orf virus
from saliva of infected pet vs contagious pustular dermatitis
lytic vs latent vs transformative infxn of EBV
stages depend on EBV gene expression. infect epithelium and B cells, shed in saliva, CD8 response vs in mem B cells, viral genes suppress viral protein synthesis, CD8 response, reactivated by immunosuppression vs cell cycle control = overridden by infected cells
how to dx EBV
sxs (lymphadenopathy,
splenomegaly, exudative pharyngitis; extreme fatigue), monospot test (heterophile ab to sheep, and horse RBCs (Paul-Bunnell Ag)), hematology (lymphocytosis, downey cells = atypical lymphocytes)
how to tx vs prevent EBV
limit activity d/t danger of ruptured spleen vs difficult d/t asx shedding
EBV proteins and transformataion
Activation of cellular oncogenes, Translocations of B cell genes, LMP 1/2
burkitt’s lymphoma vs nasopharyngeal carcinoma vs post-transplant lymphoproliferative d/o vs hairy oral leukoplakia
monoclonal B cell lymphoma, t(8,14) translocation –> moves c-myc oncogene to highly active promoter; starry sky vs EBV infected epithelial cells in Asia vs T cell suppression –> massive B cell prolif vs EBV infected epithelial cells in immunocompromised
HHV8 transmission. virulence factors?
sex. lack of T cells, latent infxn in endothel cells, transformation of endothel cells to spindle cells, prod of virally encoded cytok
what happens if there were no T cells in HHV8?
latent becomes lytic, spindle cells survive and grow
how to dx HHV8?
lesion appearance, bx, XR and bronchoscopy
HPV transmission
surfaces, sex, asx w/ shedding
HPV replication
Enter microabrasions in epithelial layer –> migrate to undifferentiated basal
keratinocytes –> infect/replicate in sq epith cells by expressing E1&2 –> inc cell # in basal and prickle layers –> specific cellular keratins made –> late proteins L1&2 made –> progeny virions made and shed –> viral DNA maintained as episomes in warts; viral DNA = integrated into host genome in ca
E5 vs E6 vs E7 oncogenes
stabilizes cellular epidermal growth factor (EGFR) –> more sensitive to growth signals vs bind to p53 and degrade it via host ubiquitin proteasome vs bind to Rb and inactivate it
why does HPV persist in basal keratinocytes?
keratinocytes = immunoprivileged; low viral ag produced there –> innate/adaptive immunity impt for fighting warts
how to dx vs tx vs prevent HPV?
Koiliocytes in ALL HPV serotypes vs imiquimod, aldara vs gardasil (6, 11, 16, 18), cervarix (16, 18), gardasil 9 (the prev 4, 31, 33, 45, 52, 58)
mutation rate, resistance, and VAP of HBV
low mutation rate; resistant to detergents, low pH, heat; VAP = HBV surface ag (HBsAg spherical and filamentous particle not infectious; Dane particle)
transmission vs at risk ppl for HBV
blood, sex, vertical, parenteral/needle vs healthcare workers, IVDU, babies of chronic HBV moms, blood/organ recipients
immune response for HBV
Ab = protective early in infxn, spherical and filamentous particles puts high ag in blood –> neutralizes ab; strong CMI can resolve infxn but cause sxs of dz
acute vs chronic vs carcinogenic HBV
Strong CMI (CD8, NK, ADCC) response –> rapid clearance; in hepatocytes w/ little to no dmg vs weak CMI response w/ delayed or no clearance; low levels of viral prod –> can clear, asx, cirrhosis, HCC vs chronic dz w/ rpted bouts of mild sxs
% of individuals that will clear infxn, be a/sx for HBV
90% clear, 5-10% become chronic; children = asx for mild dz; 25% symptomatic
how to tx vs prevent HBV
HBV immunoglobulin, RT inhibitors vs HBsAg vax
replication and immune response for HAV
replicatess in hepatocytes and Kupffer cells –> little to no dmg; shed in stool; induce CMI (CD8, NK, ADCC) response –> life long immunity
how to dx HAV?
sx/hx, confirm w/ antiHAV igM in serum
HAV vs HEV
pos ssRNA, icosahedral, no envelope –> acid stable/resistant, transmitted by contaminated shellfish, Africa vs pos ssRNA, icosahedral, no envelope –> acid stable/resistant, transmitted by contaminated water, Asia, Calici-like, 20% infxn in pregnant women
how many major genotypes for HCV?
6, in diff geographic locations
what cells does HCV infect?
hepatocytes, B cells
mutation rate of HCV
high mutation rate –> produce quasi species –> escape ab and CD8 –> CD8 can still control but cause dmg
acute vs chronic HCV
similar to HBV vs 70-75% infxn = chronic –> continuous, low level prod of virus; exac by alc or coinfxn w/ HIV or HBV
how to dx vs tx HCV?
ELISA for HCV ab, then confirm by PCR vs combo therapy (protease/polymerase inhibitor) but DEPENDS ON GENOTYPE
why is HDV called “satellite virus” and what does it cause?
b/c can’t make own attachment protein –> coinfect w/ HBV –> dz causing cytolysis of hepatocytes; causes 40% of fulminant hepatitis –> fatal
hepatocellular carcinoma
d/t combo of viral and immunological factors, continued cycles of immune-mediated dmg and repair –> genomic instability
HBV X protein
oncoprotein to transactivate cellular transcription –> inc cell growth and replication; interfere with p53 activity and mitochondrial function; Integration of HBV into host cell genome –> activation of oncogene –> increases chronic viral production
dissemination of polio
cytolytic infxn –> tissue dmg –> dz sxs; oropharaynx –> GI enterocytes –> Peyer’s patches M cells –> intestinal wall BM –> nerves to brain –> motor neurons of anterior horn
receptor for polio
poliovirus receptor (PVR) or CD155
can serum ab limit polio spread?
yes –> prevent infecting target tissue and major clinical dz
how many types of polio?
3 types, most dz caused by type 1
phases of primary infxn of polio
- asx for 90% of infxns
- abortive poliomyelitis/minor illness: M cells infected
- nonparalaytic poliomyelitis/aseptic meningitis: virus infected CNS –> back pain, muscle spasms
- paralytic polio/major illness: anterior horn cells an motor cortex of brain
coxsackie virus receptor
coxsackie adenovirus receptor (CAR), and ICAM-1 for some
at risk ppl for enterovirus D68
kids w/ asthma
clinical pres for enterovirus D68
acute: runny nose, sore throat, cough
prolonged: wheezing, fever, vomit, rash
severe: neurological, difficulty breathing
acute flaccid myelitis
from CSF: coxsackie A16, enterovirus D68 & A71
tropism vs dz vs complications for rhinovirus
epith cells, fibroblasts vs nasal epith –> release bradykinin and histamine => rhinorrhea; sxs like HA, sneeze, sore throat induced by immune mediators vs mg to resp epith and mucosa, sinusitis
why can’t rhinovirus infect beyond URT?
b/c grows best >33 degrees C
how to tx vs prevent rhinovirus
steam, pleconaril vs hygiene, no vax b/c >100 serotypes
hallmark of coronavirus
envelope w/ club shaped protein peplomers forming a corona –> protect against GI conditions
tropism for coronavirus
resp or GI epithelium w/ E2 or spike glycoprotein; grows bet <35 degrees C –> mild URT infxn and can lead to LRT infxn
are there ab for coronavirus?
yes against E2/spike glycoprotein but short lived d–> no sustained protection
SARS 1 & 2
zoonotic coronaviruses; spread by droplet but also in sweat, urine, stool; causes atypical PNA; causes cytokine storm after infecting pulm mac/DC; mortality rate depends on age
transmission, tropism, ADE of flaviviridae
by mosquito vector => arbovirus; Aedes (dengue, yellow, zika), Culex (West nile, JEEV); tropism = mono/mac, spread to brain liver, vessels, skin; have ab dependent enhancement for infxn; strong ag cross-reactivity
prevention of flaviviridae
mosquito control, live atten vax for yellow fever and JEEV
pathogenesis of dengue
4 ag distinct strains. inc vasc permeability –> plasma leakage, bleeding, dec coag
acute vs severe dengue
break bone fever, severe HA, retro-orbital pain, mild hemorrhage vs reinfxn of diff strain –> DHF or DSS; bleeding in mult organs, hypovolemic shock in DSS
ab dependent enhancement (ADE)
ab binding inc infxn –> bypasses VAP; also seen in alphaviruses b/c they co-circ with same vector and cross react
acute vs severe yellow fever
early stage; flu like vs yellow stage; black vomit
acute vs severe zika
80% symptomatic; conjunctivitis; no inc risk for woman if infected AND cleared before preg vs microcephaly, deaf/blind, Guillain Barre
acute vs severe West Nile
seasonal encephalitic arbovirus. 20% symptomatic, west nile fever: body aches, rash, fever, HA vs 1%; meningitis, encephalitis, elderly at risk
gen characteristics of chiungunya
togaviridae, alphavirus, pos ssRNA, enveloped, icosohedral capsid
transmission vs VAP vs tropism vs new vector of chikungunya
Aedes mosquito vs E2 vs broad vs aedes albopictus d/t point mutation in E1
diff b/w dengue and chikungunya?
muscle pain vs joint pain
acute vs recurrent chikungunya
high fever, HA, myalgia, arthralgia vs crippling arthralgia in small joints, 7-10d/episode, recurrent episodes for mo-yrs
gen characteristics of rubella
togaviridae
is rubella virus an only human pathogen?
yes
tropism of rubivirus
resp epith –> throughout body; extended period of viral shedding
how to get congenital rubella?
1st trimester: virus crosses placenta –> replicate in fetal tissue –> cataracts, deafness, mental retardation
immune responses to rubella
ab controls viremic spread –> IC deposition –> rash and arthralgia, CMI clears infxn; maternal ab prevent transplacental spread
rubella prevention
live atten MMR vax, give to children so they don’t infect preg
immune response to rabies
natural immunity = slow replication and immunoprivileged tissue; ab can neutralize virus but too slow to make; CMI has little role
VAP and receptors for rabies
G glycoprotein. AChR, NCAM
how to name flu strains
formal name, represent time/place/date, common name
replication of flu
HA binds to sialic acid –> virion = endocytosed –> M2 forms channel in endosome –> uncoat envelope and release capsid –> capsid goes to nucleus and replicates –> viral particles made at membrane surface –> NA claves sialic acid and release viral particles by budding
which flu strain infects both animals and humans?
A; binds to 2,3 and 2,6 linked sialic acid residues
which flu strains do ag drift vs shift?
A,B vs A
how to tx vs prevent flu
inhibit attachment (HA), inhibit uncoating (M2) for A, inhibit release (NA) for A & B vs inactivated or subunit
paramyxoviridae members
measles, mumps, parainflu
tropism for paramyxoviridae
epith, URT; cont shedding before sx
VAP for paramyxoviridae
HN or H –> hemagluttinin; fusion F protein –> fuse viral memb w/ host memb AND infected cell memb w/ uninfected cell memb; syncytia –> cell to cell spread, immune evasion
immune response to paramyxoviridae
CMI can control but cause dz sxs
host cell receptors for measles
CD46, SLAM
tropism for measles
epith –> lymphocytes, mac/DC, neurons
how to dx vs tx measles?
sxs vs passive immunoglobulin therapy
at risk ppl for RSV
premature infants, elderly, bone marrow/heart-lung transplants
RSV dzs
URTI w/ rhinorrhea, bronchiolitis, elderly LRTI w/ PNA; direct cytopathologic effects + host immune response
immune response for RSV
ab = protective only during initial infxn d/t syncytia; maternal ab = protective but too low; CMI clears infxn (mostly CD4 Th2); natural immunity wears off –> we get reinfected q 2-5y
how to prevent RSV?
maternal ab an Palivizumab against F protein
transmission vs tropism of filovirus (ebola/maraburg)
bodily fluids from infected animals vss mono/mac/DC –> myeloid cells –> cytok storm –> tissue necrosis
VAP for filovirus
G glycoprotein
initial pres of filovirus
flu like sxs
how to tx vs prevent filovirus
convalescent sera, monoclonal ab vs recombinant vax, quarantine, minimize contact w/ body fluids
early vs late sxs of hantavirus pulm synrome
fatigue, fever, muscle aches vs cough, SOB, lungs w/ fluid
how is hantavirus transmitted?
urine/feces of infected rodents, dry weather
arenaviridae
seasonal and geographical dz based on rodent reservoir, infect macs but T cells cause tissue destruction
VAP vs receptor vs coreceptor for HIV
gp160 –> 120 + 41 vs CCR5 (mac/DC, T cells) vs CXCR4 (T cells)
HIV replication
gp120 binds to CCR5 or CXCR4 –> gp 120/41 undergoes conformational change to expose fusion peptide –> Capsid released and uncoated into cyto –> 2 ssRNA genomes transcribed to 2 dsDNA molecules via RT –> dsDNA transported to nucleus and integrated into host genome by integrase –> Proviral DNA is transcribed –> host and viral mRNA go to cyto –> proteins made near cell memb by protease –> viral proteins released by budding
drug targets at HIV replication
Attachment – receptor and co-receptor antagonists
Entry – fusion inhibitors
Replication – RT and integrase inhibitors
Assembly/Release – protease inhibitors
why is HIV resistant to anti-retroviral therapy (ART)?
RT = error prone –> high mutation rate
mac vs T cell infxn of HIV
M tropic, low viral prod in latent vs lytic and latent –> dec CD4 d/t viral induced AND immune meditated lysis
in HIV, dec CD4 cells can lead to inc B cells –>
inc nonspecific ab –> hypergammaglobulinemia
how to dx vs prevent HIV
aba to gag/pol/env vs behavaior, nonoxynol 9, post exposure ART
challenges for HIV clearance
Destruction of the immune system –>opportunistic infections
Viral replication in immunoprivileged sites
Viral latency
Antigenic variation
Direct cell-to-cell transmission of virus
acute vs latent vs AIDS for HIV
CD4 > 500, flu like sxs vs CD4 200-500, M tropic R5 virus to T tropic X4 virus vs CD4 count < 200, opportunistic infxn
tropism and resistance of rotavirus
partial chemical and heat resistance, VP4 = target of neutralizing ab in vaxxed infant
why are young children more at risk for rotavirus?
b/c older children and adults have protective ab like igA
3 pathogenic pathways for rotavirus
infxn/dmg of absorptive cells, stimulation of enteric nervous system, prod of viral enterotoxin NSP4
viral gastroenteritis
extended virus shedding, alteration of intestinal villi
at risk ppl for norovirus
older children and adult b/c it binds to H blood ag (young children don’t have it)
gastroenteritis for rota vs noro
leading cause of infant vs leading cause of epidemic
HBV ag for transmission vs replication vs resolved vs vax vs healthy carrier vs infective carrier
HBV DNA vs HBsAg vs HBsAg igG and HBcAg igG vs HBsAg igG vs HBeAg w/o DNA vs HBeAg w/ DNA
nml protein v prion structure
PrPC w/ 3 alpha helices vs PrPSC w/ 2 alpha helices and 1 beta sheet
does prion have nucleic acid?
nope just protein
how does prion become bad?
spont; external src like food, injection, transplant, contact w/ contamination
challenges to elim prions
highly resistant to most disinfectants –> autoclave longer; little inflamm –> little to no clearing in body
human v animal prion dz
very slow progressing. creutzfeld-jakob dz (CJD) v bovine spongiform encephalopathy aka mad cow dz
spongiform encephalopathy
vacuolation of brain tissue d/e build up of prion fibrils that can’t be degraded. dx: proteinase K-resistant PrP, 14-3-3/tau protein in CSF
