HIV and Retroviruses - AuCoin Flashcards
Is HIV + or - sense RNA?
+
Human T lymphotrophic virus is (blank) virus causing adult T cell leukemia
oncovirus
Where is HTLV spread?
via semen, blood, and breast milk
Does HTLV have a long or short incubation period?
long, 20-50 years
Increased skin lesions, leukemia cells histologically, hepatosplenomegaly, and HYPERCALCEMIA are suggestive of:
HTLV causing ATL
What is the cause of the hypercalcemia in ATL?
increased PTHRP
Are retroviruses enveloped or neked?
enveloped
What type of Pol do retroviruses code?
RNA dep DNA Pol (REVERSE TRASCRIPTASE)
What is the fate of the DNA copy of the viral genome?
incorporated into the host genome
When the viral DNA is incorporated into the host genome it becomes a cellular gene, aka (blank)
provirus
What was the first retrovirus to be isolated?
Rous sarcoma virus; infects chx
Other cancer causing retroviruses are classified as (blank) or (blank)
RNA tumor viruses or oncornaviruses
oncoviruses alter cell growth by expressing analogues of cell growth controlling genes such as (blank)
v-src
What was the first retrovirus found to cause human disease?
HTLV
Gays, haitians, heroin addicts, and hemophiliacs were the original groups in which (blank) was seen
AIDS
What are the four criteria for retrovirus classification?
- disease they cause
- tissue tropism and host range
- virion morphology
- genetic complexity
HTLV 1, 2, 5 belong to what family?
Oncovirinae
HIV 1 and 2 belong to what family?
Lentivirinae
T/F: spumavirinae was the first isolated human retrovirus, but it doesn’t do shit to ya
true
Which family of retrovirus is associated with neuologic and immunosuppresive diseases?
lentivirus (HIV)
What is the only family of retrovirus that can immortalize or transform target tissues?
HTLV (oncovirinae)
What is the shape and size in nm of retroviruses?
SPHERICAL, enveloped, +RNA, 80-120nm in size
T/F: the retrovirus genome is +ssRNA
FALSE: TWO IDENTICAL SEPARATE COPIES OF +SSRNA WTF
Does HIV have a large or small genome?
small, only 9kb
What else is contained within the retrovirus capsid besides the weird genome?
10-50 copies of RT AND INTEGRASE, and two cellular tRNAs
What is the function of the two tRNAs in the retrovirus capsid?
they are base-paired to each genome copy to act as primers for RT
WHat post-translation mods have been made to the retroviral genome?
5’ cape and 3’ poly A tail
What is the shape of the HIV nucleocapsid?
cone/bullet shaped (D-type) or central symmetrical (C-type)
do retroviruses code polyproteins or one gene one protein?
polyproteins
what are the three major genes encoded by all retroviruses?
gag
pol
env
what does gag code for?
group specific antigen (capsid, matrix, and nucleic acid binding proteins) STRUCTURAL PROTEINS
what does pol code for?
RT, protease, and integrase
what does env code for?
envelope (glycoproteins gp120- and gp41 for HIV)
At the end of each genome there are (blank) sequences that contain promoters and enhancers to bind cellular transcription factors
long-terminal repeats (LTR)
HTLV and HIV encode virulence enhancing proteins that require what type of advanced transcriptional processing?
splicing
How are the viral glycoproteins made from the env polyprotein?
proteolytic cleavage
what is the function of gp41?
promotes cell fusion
gp120 is extensively (phosphorylated/glycosylated)
glycosylated
T/F: gp120 antigenicity and receptor specificity can drift throughout the course of a single HIV infection
true
Ag drift and change in receptor spec. of gp120 effects the immune system how?
makes it harder to clear the virus
Is it viral or cellular proteases that cleave the viral polyproteins>?
cellular proteases
why is gp120 glycosylated?
hides the important epitopes from the immune system
On the lollipop-stick model, which is 120 and which is 41?
120 is sucker and 41 is the stem
By what process does HIV enter the cell?
fusion
Where does RT take RNA to DNA?
cytoplasm
What two receptors does HIV need to bind to enter the cell?
CD4 and CCR5
What cells express CCR5
macrophages and T cells
during chronic infection, the env gene mutates and gp120 can bind what other receptor?
CXCR4, on T cells
does 41 or 120 promote fusion?
41
What sense is the DNA made by RT?
-sense
(blank) also acts as a ribonuclease H to degrade teh +RNA from the -DNA
RT
What is the error rate of RT?
1:2000
What integrates the viral cDNA into the host csome?
integrase
What sequences are duplicated that allow for integration into the host csome?
LTRs
(blank) transcribes the provirus into full length RNA
HOST RNA Pol II
What are the three proteins made from the HIV provirus?
gag
gag-pol
env
T/F: lentiviruses can survive as just plain old cDNA in the cytoplasm until the cell divides
true
Recognition of the enhancer and promoter regions in the LTR determine tissue (blank)
tropism
what is the function of rev?
regulation of RNA splicing and promotion of export to cytoplasm
what is the function of tat?
transactivation of viral and cellular genes
what is the function of nef?
decreases surface CD4 and T cell activation leading to AIDS
what is the function of vif?
virus infectivity, promotion of assembly, blocks, cellular antiviral proteins
what is the function of vpr?
transport of cDNA to nucleus, arrests cell growth
what is the function of vpu?
faciliatates virion assembly and release
(blank) polyprotein is the matrix, capsid, and nucleocapsid
Gag
(blank) polyprotein is the protease, RT, and integrase
Gag-pol
Where in the cell are viral glycoproteins translated?
the rER
Where does glycosylation of viral glycoproteins happen?
inside the rER, then goes to golgi via secretory pathway
Where doe the gag and gag-pol proteins bind?
plasma membrane
two copies of the genome and the cellular tRNA promotes (blank) of the virion
budding
The (host/viral) protease cleaves gag and gag-pol to release RT to form the virion core
viral
When does the viral protease cleave gag and gag-pol?
AFTER release from the cell
What is the major determinant of the pathogenesis and disease caused by HIV?
viral tropism for CD4 expressing T cells and myeloid cells
What myeloid cells besides T cells are infected by HIV?
monocytes, macrophages, dendritic cells, and microglial cells of the brain!
T/F: HIV production is persistent for life
true
T/F: HIV causes syncytia formation
true
T/F: CD8 function and numbers decrease
true, it ain’t all about CD4!
What cells does HIV lyse and what cells does it cause latent infection in?
lyses CD4 T cells and latent infection in myeloid cells
during sex HIV infects what surfaces?
mucosal
How is someone resistant to HIV infection?
deficient in CCR5 receptors
What are the major reservoirs and means of transmission of HIV?
persistent infection in macrophages, DCs, memory T cells, and hematopoietic stem cells
an increased release of HIV into the blood and a decrease in CD4 cells leads to what?
AIDS
what protein promotes the progression of HIV to AIDS?
nef
T/f: there are wild-type variations of nef that don’t develop into AIDS
true
What is the hallmark (from a replication standpoint) of an acute HIV infection?
large burst of virus
What causes the mono-like syndrome associated with an an acute HIV infection
the T cell proliferation and response to the HIV infection
Where does viral replication continue in the latent period?
lymph nodes
What happens to the lymph nodes and CD8 cells in chronic HIV infection?
CD8 cells decrease and lymph node architecture is destroyed
Constitutional symptoms of HIV appear at what viral titer?
1:8
Opportunistic disease appears at what viral titer?
1:128
Death occurs at what viral titer?
1:512
In AIDS, (blank)-specific immune responses are incapacitated
antigen-specific
What are the predominant cell types infected with HIV in the brain?
microglial cells and macrophages
What do the HIV infected cells i the brain release that causes neuro symptoms?
neurotoxic substances or chemotactic factors promoting inflammation
is humoral or cell mediated immunity good against viremia and at mucosal surfaces?
humoral
Onset of AIDS is what CD4 count and full blown AIDS is what count?
onset: 350
full blown: 200
What is the viral load in AIDS?
75,000 copies/mL
HIV wasting syndrome is seen in (blank)
AIDS
T/F:AIDS can cause dementia
true
WHat does AIDS dementia resemble?
Alzheimer’s
IN what percent of adults with AIDS do we see neurologic complications?
greater than 50%
T/F: enveloped viruses are easily inactivated
true
Is the prodromal period of HIV long or short?
long
T/F: HIV can be shed BEFORE any identifiable symptoms
true
In what body fluids is HIV present?
blood, semen, and vaginal secretions
Before 1985, what two groups of patients were at risk of getting HIV by accident?
organ transplant pts and hemophiliacs
What are the four reasons that HIV lab testing is done?
- ID those infected to start Tx
- ID carriers
- Confirm Dx of AIDS
- Evaluate Tx efficacy
T/F: serologic tests cannot ID recently infected people
true
When do you see large volumes of viral RNA and p24 Ag in the blood in HIV infection?
recent infection or late-stage disease
What is the ratio of CD4/CD8 in HIV pts
super low
can you isolate HIV in culture?
nope
When do you use RT PCR do Dx HIV?
If serology was positive for the Ab or for viral Ag, but HIV 1 /2 differentiation was negative or “indeterminate”
When do you start HIV treatment when CD4 is still above 350 cells/uL?
When viral load is greater than 100,000/ml
Have protein subunit vaccines to HIV been successful?
no, they only make immunity to one strain
What is the MOA of the HIV vaccine currently being studied?
production of a neutralizing Ab to the CD4 binding site of gp120
What is in the DNA vaccine for HIV?
plasmid based eukaryotic expression vectors containing gp160 and other HIV genes
the most recent HIV vaccine primes (T/B) cells with vaccinia, canarypox, herpesvirus, or a defective adenovirus vector
T cells
What are the common symptoms of an AIDS onset?
night sweats, wt. loss, oral thrush and cervical lymphadenopathy
Where is HTLV common?
Carribean islands
