virology III Flashcards
HIV characteristics- genome. what cells get infected? what kinds of genes are encoded?
lentivirus
ssRNA, pos sense (for transmission)
enveloped
undergoes reverse transcription to DNA, whcih can become integrated into host cell chromosome as a provirus
can infect non-dividing cells (macrophages)
encode structural, enzymatic, and regulatory proteins (tat, rev)
3 stages of HIV infection
- primary infection- 2-3 wks of flu-like illness, or asymptomatic
- chronic infection: clinically asymptomatic, may last years. slow decline in circulating CD4 cells. in some cases infection does not progress: long term non-progressors or elite controllers (if not detectable virus)
- AIDS. 10-12 yrs after initial infection. AIDS defining illnesses and/or decline in CD4 cells below 200 cells per microliter (normal 500-1000).
describe the pathogenesis of HIV during the 3 stages of HIV infection
primary infection: high viral replication peaking 2-4 wks post infection. loss of CD4 t cells, esp. in the gut
asymptomatic phase: initial rebound of CD4 levels. virus production and elimination occur at similar levels. steady state virus load predicts time to disease progression.
AIDS: CD4 count drops. leads to death
2 reasons for HIV genetic diversity
- massive and prolonged viral replication- so many generations
- error-prone nature of HIV replication
describe the structure of the HIV virus
central nucleocapsid cre with 2 cpoies of viral genome (ssRNA pos sense) plus core proteins and reverse transcriptase. then the virla envelope made of cellular lipids and virual envelope proteins
HIV structural elements/genes (4)
- LTR (long terminal repeat)- drives viral gene expression
- Gag- core structural protein
- Pol (reverse transcriptase) and other enzymes like protease and integrase
- Env- envelope glycoproteins involved in ceteptor binding ancd cell entry (surface glycoprotein is gp120 and TM glycoprotein is gp41)
HIV accessory genes
Vif, vpr, vpu, nef: enchance viral replication in vivo
Nef- pathogensis
Vif: counteracts action of host protector APOBEC3G
Vpu: counteracts host protector tetherin
HIV regulatory genes
Tat: trans-activates viral transcription
Rev: regulates viral mRNA transport/splicing
HIV binding and entry (3 steps with details). include drug info
- Gp120 binds CD4 receptors causing a conformational change that allows gp120 to bind to essential entry co-receptors like CCR5 and CXCR4
- Gp120 binds to coreceptors CCR5 or CXCR4, causing a second conformational change that exposes a hydrophobic fusion domain at the endterminis of gp41 (ccr5 binding inhibited by maraviroc)
- Gp41 fuses with host cell membrane (inhibited by fuzeon)
R5 strains of HIV
use the CC chemokine receptor 5 (CCR5) receptor as coreceptors for viral entry. CCR5 found on dendritic cells, macrophages, and memory T cells (esp. CD4). predominate in early infection and are typically the HIV species involved in sexual transmission.
X4 strains of HIV
use CXCR4 as a coreceptor. tend to predominate during late infection in about half of patients and can infect resting naive T cells.
how is it that some people are naturally immune to AIDS
mutant CCR5 alleles that have a 32 base deletion in CCR5 genes result in a premature stop codon and lack the CCR5 co-receptor. absence of CCR5 in homozygous mutation protects agains HIV1 transmission; heterozygosity delays disease progression. 11% of people of European descent are heterozygotes..
HIV infection: events post-entry. drugs.
partial uncoating of virus
viral core particle aka preintegration coplex is released and imported to the nucleus
reverse transcription occurs
dsDNA is generated.
DNA is integrated semi-randomly into host chromosome using viral integrase enzyme
RT inhbitors include nucleoside reverse transcriptase inhibitors (emtricitabine/ FTC), nucleotide RTIs (tenofovir), other RT inhibitors (efavirenz). integrase inhibitors (raltegravir)
provirus serves as a template for gene expression and RNA synthesis
HIV release and maturation. drugs
newly formed particles assembled and released. undergo proteolytic maturation mediated by viral protease. protease inhbitors include ritonovir, darunavir
3 factors that protect host from HIV
TRIM5alpha, APOBEC3G, tetherin
TRIM5alpha
prevents the uncoating and reverse transcription of capsid-encased viral cores
APOBEC3G
edits viral RNA and DNA by daminiating cytosines and results in genomic hypermutation. coutered bhy HIV Vif
Tehterine
prevents release of newly-formed HIV particles from the cell surface and is counter acted by Vpu
why is HAART treatment lifelong?
because HIV has productive viral reservoirs within the host that evade drug action- CNS, GI tract. or, reactivation from latent reservoirs in memory T cells. so, HAART removal leads to viral rebound.
what is meant by “HIV treatment as prevention?”
you can reduce transmission to partners of HIV+ people if you begin treating before onset of symptoms or CD4 drop
what are three new potential HIV prevention measures?
- HIV treatment as prevention
- pre-exposure prophylaxis
- microbicides
human papillomaviruses: characteristics
small dsDNA viruses
cause hyperproliferative skin lesions (warts)
some are harmless, others increase malignant disease risk
HPV pathogenesis
entry to the basal layers of skin or mucosa via microabrasions
infects stem cells in the basal layer of the epithelium
accelerated cell growth with less cell differentiation
progeny viruses produced only in superficial layers of skin
wart treatments (4)
- crytotherapy/laser therapy
- antimitotic agents- podophyllin and 5-fluorouracil
- karyolytic agents like trichloroacetic acid (TCA)
- immunostimulatory agents (topical)- imiquimod- synthetic ligand for TLR 7 and 8 to increase IFN production
HPV prevention1
- CONDOMS
- gardasil- tetravalent vaccine protecting agains HPV 16 and HPV 18 as well as HPV6 and HPV 11 (associated with 90% of genital warts). made from recombinant yeast cells expressing the major capsid protein L1 that can spontaenously form virus like particles
- Cervarix: bivalent. made in insect cells.
molluscum contagiousum virus. what does it cause? how is it spread? what species does it infect? incubation?
poxvirus that causes benign epidermal tumors
similar to vaccinia
only infects humans
spread by skin to skin contact or shared items
can incubate up to 6 mo and lesions may persist up to 2 yrs
EBV tumor associations
burkitt’s lymphoma, post transplant lymphoproliferative disease like lymphomas, Hodgekin’s disease, T cell lymphoma, nasopharyngeal carcinoma
burkitt’s lymphoma
monoclonal B cell lymphoma
endemic in some parts of Africa and common in HIV pts
multifactorial etiology that needs cofactors like immunosuppression due to AIDS, malaria and genetic rearrangements that lead to dereg of myc
post transplant lymphoproliferative disease-like lymphomas
latent EBV infection of B cells associated with rapid tumor devo in immunocompromised ppl like transplant recipients or AIDS pts
Kaposi’s sarcoma
multifocal, highly vascularized tumor composed of many cells but esp. the spindle cell.
common tumor in ppl with AIDS
highly aggressive and often fatal
before AIDS it was mostly old Mediterranean men- and it wasn’t as aggressive.
herpes (KSHV) might promote this tumor via virally-encoded cytokines and inhibitors of apoptosis
HHV-8 and tumors
infects B cells and is associted with B cell tumors in ppl with AIDS like primary effusion lymphomas and multicentric castleman’s disease. vIL-6 (virally encoded cytokine) plays a role.
hepatitis B virus and tumors
dsDNA virus
can cause chronic hepatocyte infection
chronic infection makes it 100X more likely that someone will develop liver cancer. protein X, a viral transactivator, may be a cause
merkel cell polyomavirus
small non-enveloped dsDNA virus
only 4-5 genes
tumor antigen (T antigen)causes cell transformation by inactivation of pRB and p53. MCV found in Merkel cell carcinomas- rare and aggressive skin cancer of the immunosuppressed. viral genome may be integrated into chromosomal DNA.
HTLV-1: epi and transmission
human t-cell leukemia virus
endemic in some parts of the world (japan, africa, caribbean, south america). spread via maternal milk (or sex or IV drug use, though less common). most ppl are asymptomatic but some develop ATL eventually (adult Tcell leukemia)
HTLV1 pathogenesis and diseases
infects T cells and stimulates the production of T cell growth factors like IL-2. tumors occur following a second hit and take 20-30 yrs to develop.
also associated with neurologic disease (myelopathy) called HTLV1 associated myelopathy/tropical spastic paraparesis. occurs a few yrs after infection and is progressive degenerative disease affecting the spinal cord. weakness, spasticity, inflammatory infiltrates within the CNS, demyelinating lesions of the spinal cord.
HTLV-2
may cause hairy cell leukemia but evidence is unclear. common among IV drug usesrs
