Micro: Retroviruses Flashcards
what is a retrovirus
retro- for reverse
RNA genome -> DNA -> RNA
blood borne pathogens
what are the human retroviruses
HIV (human immunodeficiency virus) - HIV1 and HIV2
Human T-cell Leukemia Virus - AKA T-lymphotropic virus
- HTLV1 and HTLV2
what is the US epidemiology of HIV
most clinically relevant of the retroviruses
bigger problem in other countries than US
roughly 1.2 million pts living with HIV in the US
highest in AA pts
most new diagnoses from male-to-male sexual contact, 2nd heterosexual contact, 3rd IV drug use
what is the pathophyisiology of HIV
viral structure - enveloped virus
viral entry: HIV infects T-lymphocytes (WBC), entry requires co-receptors, after binding to the co-receptor, GP41 is exposed -> membrane fusion
Viral replication: reverse transcriptase, integrase, host transcription and translation process are used
Viral Assembly
what is a viral life cycle
- binding
- fusion
- penetration
- reverse transcription
- transport
- integration
- transcription
- translation
- cleavage
- assembly
- budding and maturation
what is the purpose of the lipid bilayer
helps to evade the immune system, sensitive to UV, heat, compounds, etc.
what receptors are required for viral entry
co-receptors
CCR5 or CXCR4
bind envelope protein to GP120
what is reverse transcriptase
converts viral RNA into DNA
contains DNA polymerase and ribonuclease (RNase)
DOESN’T contain exonuclease (proof-reading)
highly error prone (mutations)
what is integrase
joins viral and host DNA
can penetrate a non-dividing nucleus (need activation)
occurs at random sites
uses host repair mechanisms
nearly impossible to remove
viral replication now also aided by infected cell replication
what are the host transcription and translation processes used
DNA polymerase
RNA polymerase
when occurring -> active infection
latent infection = no viral RNA production
what is part of viral assembly
HIV polyproteins contain all necessary viral components in one structure
polyproteins clump together in the cytoplasm - > stimulates budding
HIV polyproteins combine to form an immature viral particle
what do HIV polyproteins combine to form
an immature viral particle
what is protease
protease cleaves full length proteins into usable proteins -> viral maturation
what is protein cleavage
infectious
what are the treatment targets
CCR5 coreceptor antagonist (maraviroc)
Fusion inhibitor (enfuvirtide)
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
Nucleoside and nucleotide reverse-transcriptase inhibitors (NRTIs)
Integrase stand-transfer inhibitors (INSTIs)
Protease inhibitors
What is Stage 1 HIV
acute HIV infection
aka acute retroviral syndrome
acute viral illness following initial infection with HIV (flu-like)
days to weeks after initial infection
highly infectious during this period
what is the pathophysiology of acute HIV infection
rapid increase in viral load - immune system activation (antibody production)
CD8 cells (cytotoxic T cells) destroy HIV infected cells
Rapid destruction and drop in CD4 counts
what is stage 2 HIV
chronic HIV infection
Aka latent or asymptomatic HIV infection
months to years after initial infection
not all viral particles destroyed by initial CD8 attack
some HIV infected cells remain - low level replication
decreased rates of CD4 destruction
overtime, HIV viral load and CD4 counts decrease
what is stage 3 HIV
advanced HIV disease
aka acquired immunodeficiency syndrome (AIDS)
high viral loads and significantly low CD4 counts
highly infectious
high mortality rate (survival ~3 years)
what are the CD4 count for the dx of stage 3 HIV
CD4 count < 200 or presence of certain opportunistic infection(s)/cancers
occurs more frequently or are more severe in pts with compromised immune systems