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126 Cards in this Set
- Front
- Back
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Parvoviridae examples
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erythrovirus
dependovirus (adeno-associated) |
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parvoviridae appearance
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- smallest DNA virus (~20 nm)
- non-enveloped - icosahedral capsid - ssDNA genome (5 kbp - small) - inverted repeat to provide 3'-OH for DNA extension (partially double stranded) |
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What type of cell must parvoviruses infect?
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mitotically active cells
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parvoviridae life cycle
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- endocytosed by mitotically active cell
- genome uncoats and enters nucleus thru pore - ssDNA --> dsDNA in nucleus - 2 possible fates for dsDNA: t/sc & replication - t/sc: mRNA transported to cytoplasm to make protein - replication: make more ssDNA, both +/- strands - cell lysis release new virions |
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erythrovirii attack what cell type?
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RBCs
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parvoviridae transmission
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respiratory
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parvoviridae
1* infection site 2* infection site |
upper respiratory tract --> 1* viremia
bone marrow, kill precursor cells by binding to erythrocyte P Ag --> 2* viremia, can then spread to whole body |
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symptoms of parvoviridae infection
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cheek rash
transient drop in RBC and lymphocyte count (bone marrow infection) only dangerous if w/ chronic hemolytic anemia |
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adenoviridae examples
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aviadenovirus (avian)
mastadenovirus (mammalian) |
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adenoviridae appearance
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- non-enveloped
- icosahedral capside w/ fiber at each of 12 vertices - linear dsDNA genome, ~30 kbp (large), inside nucleocapsid - infected cells look like cluster of grapes |
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hallmark of adenoviridae infection
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nuclear inclusion body - high concentration of viral proteins forming crystal structure
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adenoviridae fun facts
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proteins associated w/ both 5' ends of dsDNA, used in replication
can induce IFN response by hybridizing complementary RNA --> dsRNA |
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adenoviridae life cycle
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- receptor-mediated endocytosis
- virus lyses endosome; capsid targeted to nucleus - genome and some assocated proteins enter nucleus --> early genes - early genes: TFs - induce S phase, block apoptosis, inhibits IFN - 5' terminal protein used as primer for replication - late genes: synthesized in cytoplasm, then targeted to nucleus - cell lysis releases new virions, once quantity is high (~20 hrs) |
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adenoviridae disease
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major cause of:
- respiratory ds - conjunctivitis - hemorrhagic cystitis - gastroenteritis long incubation and contagious phases |
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herpesviridae examples
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herpes simplex
varicella zoster Epstein-Barr cytomegalovirus |
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herpesviridae appearance
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- enveloped
- icosohedral capsid - dsDNA genome (very large) - linear DNA, spooled around a protein core |
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herpesviridae fun facts
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- uses a circular genome intermediate for replication
- genome contains unique and repetitive sequences - each unique region is flanked by repetitive region, allowing 4 isometric forms of HSV |
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herpseviridae life cycle
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- virus enters cell by direct membrane fusion
- viral DNA and core/tegument proteins from nucleocapsid enter nuclear pores - genome circularizes in nucleus, allowing replication - new virions released by budding (exocytosis) - direct cell-cell fusion infect adjacent cells, avoids immunity due to tight junctions |
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3 rounds of herpesviridae gene expression
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round 1: immediate-early (alpha) genes produce TF (alpha-TIF) which is required for further viral expression in nucleus
round 2: early (beta) genes allow viral DNA replication round 3: late (gamma) genes produce structural/tegumental proteins |
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herpesviridae disease
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infects mucoepithelial cells
local symptoms: pain, itching, dysuria systemic symptoms: malaise, fever, HA recurrence: 1* localy symptoms, less-severe |
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herpesviridae disease - latent infection
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- infects neurons by retrograde transport; reinfects by anterograde transport
- early stages similar to normal infection: virus binds to cell receptors, enters cell, gets uncoated & genome is target to nucleus - only Latency Associated Transcripts (LATS) are detected |
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VZV
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varicella zoster virus
alpha-herpesvirus: chickenpox & shingels latently infects neurons |
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EBV
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Epstein-Barr
gamma-herpes virus: mono latently infects B cells |
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CMV
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beta-herpesvirus; congenital disease
infects epithelial and immune cells |
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HHVS
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human herpesvirus 8
gamma-herpesvirs: AIDS-associated |
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treatment for herpesviridae
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Acyclovir (nucleoside analogues)
- incorporated into replicating DNA, but terminates the chain - lacks terminal sugar and -OH group |
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Picornaviridae examples
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enterovirus
- polio - coxsackie -chovirus rhinovirus hepadnavirus |
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picornaviridae appearance
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- non-enveloped
- icosahedral capside w/ 5 surrounding protomers (each includes VP1-4) - + RNA genome w/ 7 kbp, 5' viral proteins and 3' poly-A |
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picornaviridae (e.g.: poliovirus) life cycle
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- virus binds to ICAMR, forms channel thru plasmalemma
- viral RNA enters cytoplasm - genome has one large ORF encoding one huge polyprotein - host protein recognize 5' VPg end & translates - viral replicase makes - RNA strand, which can make new + strands - once viral RNA inserted into procapsid, VP --> VP2 and 4, forming mature capsid - cell lysis releases virions |
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what does poliovirus polyprotein include?
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capsid proteins
proteases viral replicase VPg protein |
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picornaviridae transmission
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oral-fecal
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picornaviridae disease
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early infection: viremia, minor illness; often stops here
late infection: spreads to lymphatics and CNS --> meningitis & paralysis almost all infections are asymptomatic |
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rhinovirus characteristics
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not stable in acidic environment
limited to respiratory tract |
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enterovirus characteristics
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includes polio, coxsackie, echovirus, hep A
stable in acidic enritonment initally replicate in oropharynx, then enter bloodstream replicates in gut |
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treatment for picornaviridae
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Pleconaril
- drug that binds to canyons in viral capsid - blocks entry into cell |
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coronaviridae example
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corona virus
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cornoaviridae appearance
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enveloped w/ pointy glycoproteins that form a crown
+ RNA genome w/ 30 kbp loosely-helical nucleocapsid |
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coronaviridae fun facts
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+ RNA virus
major corna virus proteins: E2, E1, N, L, H1 does not have one large ORF - makes subgenomic mRNA, instead |
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coronaviridae life cycle
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(1) translation of polymerase from + RNA
(2) polymerase synthesizes - RNA (3) synthesize subgenomic + mRNA and + RNA from - RNA strand RNA genome associates wth N protein virus buds into ER, sent to golgi, then exocytosed |
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N protein
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nucleic binding protein
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are coronaviridae directly exocytosed?
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no - bud into ER
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coronaviridae transmission
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aerosol transmission
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coronaviridae disease
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assocated with URT infections
often self-limiting |
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SARS
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severe acute respiratory syndrome
coronavirus host range increased from most coronaviridae & can grown in tissue culture (not normal) quicker replication avoids immune system viral PNA (lower resp tract) |
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orthomyoviridae example
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influenza
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orthomyxoviridae appearance
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- enveloped
- -- RNA genome (8 segments), irregularly shaped |
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4 orthomyxoviridae proteins
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hemaagglutinin (HA)
neuroaminidase (NA) nucleoproteins (NP) channel proteins (M2) |
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role of hemagglutinin in orthomyxoviridae infection
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binds RBCs and makes them clump
has 2 regions: attachment & fusion |
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role of neuroaminidase in orthomyxoviridae infection
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cleaves sialic acid from host glycoproteins
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role of nucleoproteins in orthomyxoviridae infection
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assocated with segmented genome
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role of channel proteins (M2) in orthmyxoviridae infection
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promotes uncoating and viral release
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which 2 orthomyxoviridae proteins are majorly antigenic?
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HA
NA |
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stages of influenza infection from outside cell to nucleus
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HA attaches to sialic acid of CM glycoproteins
nucleocapsid enters cell by receptor-mediated endocytosis endosome's acidity induces conformational change of HA, exposing fusion region viral envelope fuses w/ endosome mb nucleocapsid, now in cytoplasm, targets to nucleus |
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stages of influenze infection from nucleus to new virions
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in nucleus, viral transcriptase (replicase) creates + RNA from - RNA
influenza steals 5' ends of cellular mRNA to use as primers viral mRNAs translated in cytoplasm or ER (for membrane proteins) Er/golgi insert HA, NA, and M2 into cell membrane nucleocapsid assocates w/ membrane proteins budding releases virions at APICAL surface only |
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influenza transmission
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aerosol transmission --> respiratory tract
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influenza disease
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STRONG immune response causes many symptoms (fever, cough, etc.)
direct cell death of mucous secreting and cilated epithelium possible bacterial infections, PNA & CNS damage |
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influenza treatment
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Amantadine & Rimantadine:
- neutralize pH of endosomes (blocking HA's fusion) - blocks M2 channels: no H+ influx, inhibits viral uncoating & no nuclear entry Tamiflu: blocks NA, which is required for viral release |
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influenza evolution:
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antigenic drift:
- gradual change in antigenicity - due to RNA polymerase inaccracy - more common - leads to annual epidemics antigenic shift - rearranging 8 genomic segments - due to mixed viral infection - less common - causes pandemics |
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Avian Flu
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involves antigenic DRIFT that causes it to infect humans (dead-end host)
once it can jump human-to-human, it will be extremely deadly |
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Arboviruses (stands for what?)
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Arthropod-Borne viruses
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Arbovirus examples
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Togavirus
Flavivirus |
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Arbovirus appearance
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enveloped (mostly)
icosahedral capsid + RNA genome |
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arbovirus fun facts
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never human-to-human transmission (dead-end host); too low of viremia titer
can have subgenomic mRNAs |
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arbovirus life cycle
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female mosquitoes acquire virus from their lunch; infects their midguts and saliva
virus transmitted in later lunches targets macrophages, vascular endothelium, LNs and liver causes lytic or persistent infections |
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3 diseases caused by arboviruses
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alphavirus/flavivirus disease
Dengue fever West Nile Virus |
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Alphavirus/Flavivirus disease
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1* viremia
- mild systemic disease - 2-3 days after infection - IFN secretion may cause flu0like symptoms - most infections resolved 2* viremia - encephalitis, hemmorhage - replicates in Mphages due to Abs enhancing viral uptake infection often seasonal due to insect vectors |
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Dengue fever
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involves 2 incubation periods
- extrinsic incubation: when mosquito 1st acquires virus until it transmits it (7 days) - intrinsic incubation: when mosquito transmits it until viremia occurs (7 more days) |
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West Nile Virus
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Flaviviridae family
Birds <--> mosquitos --> humans (dead-end host) |
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Rhabdovirus disease, aka:
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rabies
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rhabdovirus appearance
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enveloped
ssRNA (-); bullet shaped helicial nucleocapsid |
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rhabdovirus reservoirs
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raccoon, skunk, bat, fox, some domesticated animals
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rabies
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virus replicates in muscle tissue
enters PNS, ascending neurons to CNS replicates in DRG and infects brain |
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Filovirus examples
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Marburg
Ebola |
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Filiovirus characteristcs
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enveloped, - RNA
severe hemmorhagic fevers assumed to have an animal reservoir |
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retrovirus families
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oncovirinae
lentivirinae (e.g.: HIV) |
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retrovirus appearance
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envelope w/ 2 glycoproteins: gp41 & gp120
capsid containing: + RNA genome reverse transcriptase integrase tRNA on 5' |
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what capsid protein is used for HIV Ab testing?
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capsid protein p24
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retrovirus fun facts
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has 2 identical copies of RNA genome
repeat sequences on each end of genome unique sequences - internal part of genome |
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4 retrovirus proteins
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gp120
gp41 p17 p7/p9 |
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gp120 function
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attaches to CD4 TCR and CXCR4 co-receptor
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gp41
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transmembrane protein
conformational change --> insert into T-cell --> fusion |
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p17
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matrix protein below membrane
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p7 & p9
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nucleic acid binding proteins
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retrovirus infection process from outside cell to nucleus
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gp120 binds to CD4 --> conform. change --> recruits CCR & CXCR4
gp41 inserts into membrane --> fusion nucleocapsid enters cytoplasm tRNA on 5' end acts as primer to synthesize cDNA --> RNA/DNA hybrid RNA strand digested by RT's RNase activity 2nd strand of DNA synthesized new dsDNA (proviral DNA) has LTR at each end w/ promotor & polyA signals proviral DNA enters nucleus |
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retrovirus infection process from nucleus to new virion
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proviral DNA randomly integrates into genome via integrase
inegrated proviral DNA copied by host mchinery --> viral RNA & protein transcription: full-length RNA processed into shorter mRNAs translation: GAG and POL cut from same polyprotein; ENV from spliced mRNA buddding releases nucleocapsids maturation of virion occurs AFTER budding via viral protease |
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viral RNA always uses what enzyme?
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cellular RNA polymerase II, which recognizes 5' promoter and 3' poly-A
LTR sequence is critical |
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retrovirus disease
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infects CD4 T cells and APCs
causes loss of T cells by CTL-cytolysis of infected cells persistent infection - due to integrated genome - lytic if many proteins produced latent infection - when no viral RNAs produced - can restart later once T cells are low |
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HIV testing
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viremia: test for free virus (p24 capsid protins) or proteins (gp120, gp41)
latent infection: test for Abs or decreased T cell function ELISA: patient serum applied to dish of Ags - detects serum Abs Quick assay: useful for screening, but Se/Sp issues Western Blot: more sensitive PCR: v. sensitive: looks for viral nucleic acids |
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retrovirus tx
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nucleoside analogues: Azidothymidine - missing 3' OH, ends chain
non-nucleoside RT inhibitors - stop viral enzyme RT protease inhibitors: stops final step of virion maturation (cleaves GAG & POL) fusion inhibitors: blocks gp41 mediated fusion |
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GAG gene
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structural matrix capsid genes
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POL gene
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protease, RT, integrase
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ENV
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gp120 and gp41 (specific for HIV)
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Hep A virus family
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picornaviridae
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Hep A appearance
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non-enveloped
icosahedral capsid + RNA genome with 5' VPg |
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Hep A, aka:
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HAV
"infectious hepatitis" |
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Hep A life cycle
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initial replication in oropharynx, intestine
grows in liver cells |
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Hep A disease
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oral-fecal transmission
symptoms due to immune response; lysis of hepatocytes by T and NK cells (ADCC) many asymptomatic infections; no persistent or chronic infection causes 40% of acute hepatitis |
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Hep A prevention
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killed viral vaccine
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Hep A treatment
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immune globulin for early stages
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Hep B virus family
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Hepadnaviridae
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Hep B appearance
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enveloped
DNA genome; small |
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Hep B fun facts
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known as "serum hepatitis" b/c surface Ag abundant in serum
uses RNA intermediate |
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Hep B life cycle
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attaches, fuses, core enters cytoplasm, then nucleus
t/sc'd RNAs enter cytoplasm to make protein or RNA/DNA hybrids DNA t/sc'd to RNA, then RT'd to ssDNA dsDNA formed in capsid budding releases mature virion & Dane Particles |
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Dane Particles
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not infectious
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Hep B transmission
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sex, blood and birth
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Hep B disease
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many symptoms due to immune response, including jaundice/icterus
chronic: persists in liver, leading to cirrhosis or cancer; severe if combined with HDV |
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Hep B prevention
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recombinant subunit vaccine
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Hep B treatment
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immune globulin to block early stages or mother-baby transmission
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Hep C virus family
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flaviviridae
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Hep C appearance
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enveloped
+ RNA |
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Hep C fun facts
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good at evading immune system: PCD, IFNs
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Hep C disease
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major source of chronic hep infections
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Hep C prevention
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no vaccine
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Hep C treatment
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combined IFN-alpha & ribavirin
only 50% effective |
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Hep D virus appearance
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circular ssRNA genome
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Hep D fun facts
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"D" is for "defective" - requires HBV surface Ag HBsAg to form envelope
HBsAg secreted as Dane Particles |
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Hep D transmission
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sex, blood
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Hep D disease
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severe if infects after chronic HBV established
less severe if infection occurs together |
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Hep D acute hepatitis
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CMI and inflammation
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Hep D chronic hepatitis
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cirrhosis, delta infection
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Hep D prevention
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recombinant subunit vaccine
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Hep E virus, aka:
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HEV
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HEV appearnce
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non-enveloped
+ RNA |
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HEV fun facts
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"E" is for "enteric"
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Hep E transmission
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oral-fecal
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Hep E disease
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acute infection ONLY - no chronic hep
higher mortality rate than other HVs - v. high in pregnant women (20%) no vaccine or tx |
