Retroviruses and HIV-1 Flashcards
DNA sequence that can change its relative position within the genome of a single cell
transposable element
copy themselves in two stages, from DNA to RNA by transcription then from RNA to DNA by reverse transcription
retrotransposons
cut from the genome by a transposase and inserted into another region of the genome
DNA transposons
retroviruses are (enveloped/noneveloped) viruses and are the only ______ viruses that contain a ________ enzyme
enveloped
diploid
reverse transcriptase
retrovirus replicates through a double stranded DNA intermediate known as _______ that integrates randomly into the host cell chromosome
provirus
- virus transmitted primarily by breastfeeding, sexual, and contaminated blood, solid organ transplants
- infects CD4 T cells lifelong
- most infected patients remain asymptomatic
HTLV-1
HTLV-1 causes ______ when infected at birth or early in life
adult T cell leukemia
the envelope glycoprotein of HIV-1 is responsible for virus binding to the _______ and co-receptor molecules on the surface of susceptible cells
CD4 receptor and co-receptor
the transmembrane component is responsible for the _______ of viral and host cell plasma membrane during entry
fusion
chemokine receptor used by HIV-1?
CCR5
the HIV-1 glycoprotein is a target for what antibodies?
gp120, CD4, gp41, CCR5 coreceptor
virus gp120 binds _____ receptor, induces conformational change that allows glycoprotein to bind ______
CD4
CCR5
when _____ undergoes conformational change, allows fusion peptide to attach to lipid bilayer and fusion event
gp41
converts immature virus particle to mature virus particle? last step of maturation
viral protease
early on retrovirus can affect ________, attacking T cells with CCR5 on surface, then migrates to spleen, brain, lung, and kidney
GALT
the _______ is the level of viremia at the end of the acute stage of infection, and the higher the number the faster the progression to AIDS
set point
mean time from infection to AIDS is approximately ______
10 years
clinical findings of primary or acute stage oh HIV infection?
headache, muscle aches, sore throat, fever, swollen lymph nods, CNS disorders, pneumonitis, diarrhea or GI complaints
course of primary or acute stage of HIV infection?
lasts for weeks, get lymphadenopathy/lethargy/malaise for months
lab findings in acute stage of HIV infection?
lymphopenia, thrombocytopenia, CD4/CD8 ratio decreases due to active depletion of CD4 and expansion of CD8, p24 antigenemia, virus may be present in CNS
HIV asymptomatic period is a period of __________, however there is _______ virus replication during this period
clinical latency, constant
during asymptomatic period there is constant turnover of? toward end there is an increase in due to deterioration of immune system?
infected T cells, viral loads
immune evasion: external protein _______ of HIV is covered with glycosyl groups, which are identical to host proteins
gp120
_____ protein downregulates MHCI
nef
AIDS is defined as being HIV-1 positive and CD4 T cells below? or being HIV positive and?
200 cells/uL, AIDS defining condition
common opportunistic infections of AIDS?
protozoa-toxoplasmosis cryptosporidosis
fungal: pneumocystis jiroveci, candidiasis, histoplasmosis, coccidiomycosis
bacterial: mycobacterium, salmonella
viral: CMV, HSV, VZV, JC virus
time periods:
rapid progressor?
typical progressor?
long term non progressor?
2-3 years
10 years
7-25 years (viremic controller or elite controller)
HIV rapid progressors have a high ________, represent about 10% of individuals, develop AIDS in about _____ years without CART, have an absent or weak CTL and antibody response
viral set point
2-3 years
HIV long term non-progressors maintain elevated CD4 T cell counts in absence of cART for _________ years, represent 2-5% of HIV patients, and maintain low levels of ______
7-25 years
viremia
HIV viremic controllers achieve virologic control is range of ________ copies, maintain elevated CD4 T cell counts typically above ______, but with time will likely lose T cells
200-2000 copies
less than 500 cells
elite suppressors or controllers maintain ________ viral loads without cART, represent less than 0.5% of patients, virus can be _______, generally have strong CTL responses
undetectable
isolated
lab diagnosis of HIV: antibody antigen test to look for _____ and _____ antigen, confirmed with a _______ assay
HIV1/HIV2 antibodies, p24 antigen
multispot assay
obstacles in HAART:
- virus persists in ________ CD4 T cells
- virus replication _______ in almost all patients after discontinuation
- unlikely that pool of ______ virus can be completely eliminated
resting memory
rebounds
latent
mycobacterial disease:
- transmitted by ______
- taken up by alveolar _______ and form _______ in lungs where bacteria can go dormant
- reactivated to form?
aerosols
macrophages, granulomas
M tuberculosis, M avium complex (MAC) into disseminated, lymphadenitis, or pulmonary disease
- fungus, colonizes normal host, can cause severe pneumonia in immunocompromised
- prophylactic trimethoprim sulfamethoxozole
pneumocytis jiroveci
- most common fungal infection in HIV infected patients
- white stuck on plaques on tongue, buccal mucosa, palate
- esophagitis and skin
candida albicans
- dsDNA enveloped virus
- enters latent state in monocytes and can be reactivated
- causes retinitis, GI tract, pulmonary, CNS, myelopathy, bone marrow suppression
cytomegalovirus
- enveloped DNA virus
- infects B lymphocytes and epithelial cells of throat
- 90% of adults in US have antibody to virus
EBV hairy leukoplakia
opprotunistic malignancies?
Kaposi sarcoma HHV8, CNS lymphoma due to EBV, Hodgkin lymphoma, HPV cervical and anal squamous cell carcinoma
- parasite transmitted through undercooked meat and cat feces
- CNS disease via reactivation
- headache, confusion, motor weakness, fever
- ring enhancing lesions on MRI, cysts
toxoplasmosis
- causes meningoencephalitis
- fever, malaise, headache with neck stiffness, photophobia, vomiting
- abnormal CSF
cryptococcus neoformans
- caused by papovavirus JCV
- reactivation –> cognitive impairment, focal motor deficits, seizures
- ARV to re-establish host immune system
PML
AIDS virus in CNS evolves to become largely _______ tropic that targets ______ cells
macrophage, microglial
- white matter pallor, microglial nodules, multinucleated giant cells
- 40% reduction in frontal and temporal neurons
- memory deficits, impaired executive function, poor attention, mental slowing, apathy
AIDS related dementia complex
