HIV Flashcards
Retroviruses genome and strucutre
+RNA
enveloped
important enzyme of retroviruses
Contain reverse transcriptase enzyme
- Copies RNA into DNA
chronic nature of retroviruses
Cause chronic disease long after infection
- Due to integration of viral DNA into host
chromosome
cause of AIDS
HIV (human immunodeficiency virus) is a retrovirus
that causes AIDS (acquired immunodeficiency
syndrome)
overall decline of HIV
newly infected and deaths related to HIV are decreasing
retrovirus capsid geometry
conical
important envelope glycoproteins of retroviruses
gp41 and gp120
provirus
DNA copy of viral RNA
DNA copy is inserted into the host genome
HIV adsorption and penetration:
initial and late infection?
tropic nature?
M tropic (initial infection):
cells of macrophage lineage
Receptor/coreceptor: CD4 and CCR5
T tropic (later during infection):
T cells
Receptor/coreceptor: CD4 and CXCR4
HIV adsorption mechanism
resistance?
Viral ENV protein gp120 binds to cellular receptor CD4 and to coreceptor CXCR4 or CCR5
Coreceptor interaction essential for gp41 contact and viral fusion with host cell.
Small number of resistant people - lack the coreceptors
HIV penetrance
due to membrane fusion promoted by gp41, facilitated with coreceptor binding gp120
gp41 undergoes conformational change
HIV genome replication parts
3 parts
1: synthesis of viral DNA copy
2: integration into host genome
3: transcription of viral DNA into more RNA
part of 1 of HIV genome replication
Part 1: synthesis of viral DNA copy
Cellular tRNA used as a primer by reverse transcriptase
Several steps are required to create a double-stranded DNA copy of the positive sense, single-stranded RNA genome
Reverse transcriptase (RT) synthesizes one strand of DNA using viral RNA as the template.
Reverse transcriptase (RT) synthesizes the other strand of DNA using the newly created viral single DNA strand above as the template.
importance of RT
RT enzyme is the major target for anti-HIV drugs
RT enzyme is error prone (1 error every 10000 nts!) ~1 error per genome, allows immune evasion
HIV genome replication part 2
part 2: integration of viral DNA copy into host cell genome
Promoted by viral integrase enzyme
HIV replication part 3
part 3: transcription of integrated viral DNA copy to create more viral RNA for assembly
Viral DNA is transcribed into RNA by host cell RNA polymerase II
HIV protein expression and viral assembly
Viral RNA serves as mRNA for translation AND Viral RNA serves as the viral genome that is packaged into virions
Translation creates viral polyproteins, cleaved by proteases to mature sizes
Viral assembly occurs at plasma membrane. Virions acquire their membrane by budding of nucleocapsids from the plasma membrane.
HIV accessory factors, important ones?
mod host cell functions
nef and vpu
nef
decreases expression of MHC class I molecules on the surface of an infected cell, preventing killing by cytotoxic T cells
vpu
reduces cell surface CD4 expression and enhances viral release
Long terminal repeats (LTRs) of the HIV genome
repsond to? create?
Transcriptional promoter (upstream LTR) and terminator (downstream LTR)
Promoter responds to host cell signals and can also be relatively dormant, creating the latent state that is an important characteristic of HIV
HIV entry
routes?
enters as?
Virus may enter through:
microabrasions on mucosal surfaces
needle punctures (IV drug users)
intact mucosal surfaces
Virus may enter as:
part of an infected cell (macrophage, lymphocyte, spermatozoa)
free virus
HIV replication during the chronic phase of infection after burst of viral replication that occurs during initial infection, cell populations
99% infected cell are CD4 Tcells with less than 1% being macrophages and resting CD4 cells
the less than 1% populations are responsible for viral latency
initial HIV pathogenesis
Note initial contact is with macrophage lineage cells.
Infect/stick to dendritic cells
transport to lymph node - contact with CD4 T cells for chronic effects
chronic HIV pathogenesis
loss of DTH mediated by CD4: important for controlling fungal and intracellular pathogens
(bacterial and viral)
neurological symptoms of chronic HIV possibly from?
basis is not well understood
- possibly due to viral infection of neurons
- possibly release of substances by other cells that promote inflammation in brain
viral load, cd4 count and Ab level in HIV
initial high viral load will fall as a result of Ab response, but CD4 levels fall slowly before increase in viral levels later on with a decreased Ab
criterion for AIDS.
<200 CD4 T-cell/mm3 is the
Patients with higher CD4 Tcell counts are also considered to have AIDS if they display AIDS indicator
conditions
AIDs indicators conditions
Candidiasis of the bronchi, trachea, or lungs
Candidiasis, esophageal
Kaposi sarcoma
Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, pulmonary or extrapulmonary
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jiroveci (formerly carinii) pneumonia (PCP)
Transmission of HIV
Transmission occurs by direct exposure of persons bloodstream to body fluid containing virus. HIV is found in the blood, semen, or vaginal fluid of someone who is infected with the virus.
HIV and casual contact
not transmitted by casual contact (touching, etc.) (or even kissing, sneezing, bug bites, etc.)
HIV and healthcare workers’ risk
There is a risk for health care workers but transmission even through needlestick is poor
(less than 1% of exposures show seroconversion)
AIDS defined
- progressive destruction of CD4+ cells leads to collapse of immune system
- patient susceptible to opportunistic infections (see AIDS indicator conditions)
Central nervous system disease also
associated with AIDS
dementia
AIDS-related cancer
• Kaposi’ s sarcoma
– caused by human herpesvirus 8
HIV treatments
– antiviral agents
• nucleoside analogue reverse transcriptase (RT) inhibitors
• nonnucleoside RT inhibitors
• protease inhibitors
• Fusion-penetration inhibitors (target gp41)
HIV Vax
none, ongoing search
HIV evasion of immune response
plasma virus will continually evolve with replication error by RT, causes neutralizing Ab to act as a selective pressure against different antigenic variants
if Ab from a later period of infections were used with earlier plasma viruses better neutralization could be seen
Other human retroviruses
diseases?
human T-cell lymphotropic viruses (HTLVs) -I, -II, -III, and -IV
HTLV-I: causes adult T-cell leukemia and lymphoma
II,III and IV: no known diseases
