Exam 3 - Retroviruses Flashcards
Retroviruses
Endogenous definition
-8% of human genome, carried
40 million yrs
-transmiss via germ cell line
Retroviruses
Exogenous definition
- from primates
- lentiretroviruses (HIV 1 and 2)
- deltaretroviruses (HTLV 1 and 2)
Retroviruses
Morphology, general
- enveloped (bud from host)
- 2 copies + sense RNA
Retroviruses
path, general
- use reverse transcriptase to make DNA provirus
- DNA integrates in host genome w/ integrase
- transcription by host cell
Retroviruses
lentiretrovirus (HIV)
transmiss/epi
- sex, blood, True Blood on HBO, sin
- most primates (cpz, sm) act as asx viremic res
- cross-species transmission
- rhesus macaques are symptomatic
- SIVcpz (chimp) ->HIV1 (worldwide)
- SIVsm( mangabey) ->HIV2 (W. Africa, India)
- HiV entered human in early 1900s
Retroviruses
lentiretrovirus (HIV)
strains
- US: Group M, Clade B
- Other: Groups M, N, O
- Clades: regional gene variants
Retroviruses
lentiretroviruses (HIV)
gene products
- hopefully don’t hafta know these…
- tat: elongation
- rev: export
- nef: downregs host CD$ and MHC1 expresssion
- vif: infectivity
- vpu: downregs CD4 expression, increase release
- vpr: promotes nuclear import of DNA pro-virus
Retroviruses
lentiretrovirus (HIV)
path
attachment, fusion, entry, reverse transcription,
nuclear translocation, integration, transcription,
RNA processing, translation, assembly, budding,
maturation
Retroviruses
deltaretrovirus (HTLV)
transmiss/epi
- sex, blood. vert tranmiss rare.
- HTLV1 endemic in Japan, Caribbean
- HTLV2 US, EU, SEAsia, Amerindians, C. Africa
Retroviruses
deltaretrovirus (HTLV)
path
- infects T, endothelium, fibroblasts
- oncogenesis
- lymphoma, myelopathy (paraesis)
Retroviruses
HIV
epi
- 35 mil worldwide, 1.3 mil N. America
- most HIV is HIV1
- worldwide
- US higest prev in DC! Look around!
- on the rise again in MSM
- disproportionate prev in black women
- stop glancing at Kristian and Cristal
Retroviruses
HIV
transmision
- sex, blood, True Blood, sin
- being friends with gay people
- vertical (maternal-fetal) 30% w/o anti-HIV
- breast feeding
Retroviruses
HIV
risk factors
-besides the obvious:
-genital ulcer dz, uncircumcised,
traumatic sex, anal sex, cervical
ectopy, CCR5 phenotype
Retroviruses
HIV
immune response
- CD8 most imp’t immune response,
- antibodies
- innate host defenses
Retroviruses
HIV
path
-trapped in lymph nodes by follic dendritic cells
-infect lympocytes and macrophages
-lymph node decompensation
-CD4 depletion via: cytopathicity, apoptosis,
syncitia, CD8 and NK recruitment
-opportunistic infxns
Retroviruses
HIV
dx
- prelim ELISA
- confirmatory Western Blot or Multispot
- PCR for recent (<2 wks) infxn
Retroviruses
HIV
acute/primary sx
- 50-90% of infected
- 2-4 wks after exposure
- mono-ish, poss meningitis
Retroviruses
HIV
AIDS dx
- CD4 count <200 cell/uL
- avg onset 10 yrs after infxn, untreated
Retroviruses
HIV
AIDS clinical pres
- HIV encephalopathy/dementia
- peripheral neuropathy, vacuolar myelopathy
- a milli secondary infxns
- reemergence of latent infxns
Retroviruses
HIV
AIDS 2* infxns
- pneumocystic jirovecii pneumonia (CD4<100)
- esphoageal candidiasis (varies directly w/ immunosupression)
- chronic mucocutaneous HSV
- histoplasmosis
- progressive multifocal leukoencephalopathy
- TB
- bacterial pneumonia
- cryptosporidosis, isosporiasis
- extraintestinal strongyloidiasis
Retroviruses
HIV
AIDS 2* malignancies
- Kaposi’s sarcoma (HHV8)
- lymphoma (non-hodg, burkitts, CNS; EBV)
- cervical (HPV)
- rectal squamous cell carcinoma (HPV)
Retroviruses
HIV
AIDS other clin
- wasting syndrome
- thrombocytopenia
- renal dz
- cardiomyopathy
Retroviruses
HIV
AIDS surrogate markers
- CD4 count
- systemic sx (fever, chills, night sweats)
- oral candidiasis, oral hairy leukoplakia
Retroviruses
HIV
tx
- begin tx when CD4100,000
- reverse transcriptase inhibitors
- protease inhibitors
- integrase inhibitors
- CCR5 receptor antagonists
- inhibitors of HIV entry