HIV- Exam IV Flashcards
Describe genomic structure of HIV:
positive strand RNA virus
HIV is considered a ____ virus
retrovirus
Why is HIV considered a retrovirus?
because it contains reverse transcriptase enzyme that copies RNA into DNA
HIV causes chronic disease long after infection due to:
integration of viral DNA into host chromosome
Describe the structure of the retrovirus HIV: (4)
- enveloped virus
- HIV matrix proteins surround nucleocapsid
- core conical nucleocapsid
- envelope glycoproteins
HIV has ____ on the surface of the virus
adhesin
The adhesin on the surface of HIV engages with:
a CD4 receptor and a coreceptor (either CCR5 or CXCR4)
In HIV adsorption and penetration, the use of a coreceptor will:
dictate the types of cells that will become infected
Initial HIV infection =
M tropic
HIV infection infecting cells of macrophage lineage with coreceptor CCR5:
M tropic (initial infection)
HIV infection infecting T-cells with use of coreceptor CXCR4:
T tropic (later during infection)
Later HIV infection =
T tropic
What is the adhesin on the surface of HIV that binds to CD4 receptor?
viral ENV protein gp120
In HIV infection, when the coreceptor is engaged, what does this allow for?
The virus to become more closely positioned to the cell surface/membrane
After the coreceptor is engaged in HIV infection, allowing for close proximity of virus to cell surface/membrane, what occurs?
a second viral protein gp41 comes into contact with host cell membrane to promote viral fusion
What would occur in the absence of coreceptor binding by gp120?
low infectivity of HIV
How was it discovered that a coreceptor is necessary for infectivity of HIV?
a small number of individuals in the population are resistant to HIV infection
In HIV infection, coreceptor interactions is essential for:
GP41 contact and viral fusion with host cell
The individuals in the population who are resistant to HIV infection lack:
coreceptors
HIV penetration is due to:
membrane fusion promoted by gp41
retroviruses like HIV do not undergo:
an initial phase of translation
The penetration of the nucleocapsids into the cytoplasm of the host cell has to do with the interaction of:
viral gp41 protein with host cell membrane
Once the gp120 binds to the CD4 & to the coreceptor this allows the gp41protein to be close enough to the host cell membrane to undergo a ____ that causes part of the gp41 protein to engage both the _____ but also the ____.
conformational change; viral envelope; host cell membrane
Following Gp41 engagement with both viral envelope and host cell membrane, a subsequent conformational change pulls the viral envelope and host cell membrane together to ____ and allows the delivery of ____.
fuse; the viral nucleocapsid into host cell cytoplasm
In HIV infection, once the nucleocapsid is present with the host cell cytoplasm the first major step of viral replication involves the use of:
reverse transcriptase enzyme
What is the first step of completed by reverse transcriptase in HIV infection?
takes positive stranded RNA and copies it into a DNA strand
What is the second step of action completed by reverse transcriptase in HIV infection?
takes the DNA strand and copies it into a second complimentary strand to create a double stranded DNA complex
what is the first part of HIV genome replication?
synthesis of viral DNA copy
Reverse transcriptase synthesizes ___ using viral RNA as the template
one strand of DNA
Reverse transcriptase synthesizes ___ using the newly created viral single DNA strand as the template
the other strand of DNA
What is the major target for anti-HIV drugs?
RT enzyme
RT enzyme is very ___
error prone
Because RT enzyme is extremely error prone, this results in:
many HIV variants
When synthesizing the viral DNA copy, cellular tRNA is used as a ____ by reverse transcriptase
primer
Ultimately part 1 of HIV genome replication results in:
A copy of the viral RNA now in the double stranded DNA
Part 2 of HIV genome replication is:
integration of viral DNA copy into host cell genome
In part 2 of HIV genome replication: integration of viral DNA copy into host cell genome, this step is promoted by:
integrase
Part 3 of HIV genome replication is:
transcription of integrated viral DNA copy to create more viral RNA
In part 3 of HIV genome replication: transcription of integrated viral DNA copy to create more viral RNA, the viral DNA is transcribed into RNA by:
host cell RNA polymerase II
HIV protein expression and viral assembly:
____ serves as mRNA for translation
___ serves as the viral genome that is packaged into virions
viral RNA
HIV protein expression and viral assembly:
Viral assembly occurs at the ___.
plasma membrane
HIV protein expression and viral assembly:
Virions acquire their membrane by ____ from the plasma membrane
budding of nucleocapsids
HIV protein expression and viral assembly:
Translation creates:
viral polyproteins
HIV protein expression and viral assembly:
Viral poly proteins get cleaved to final mature sizes by:
viral protease
during an HIV infection _____ can modulate the host cell and assist the virus in types of cells it can infect
HIV accessory factors
during HIV infection, functions to decrease expression of MHC class I molecules on the surface of an infected cell, preventing killing by cytotoxic T-cells
nef
What is the ultimate action of nef?
prevent killing by cytotoxic T-cells (by decreasing expression of MHC class I molecules on surface of infected cell)
during HIV infection, functions to reduce cell surface CD4 expression and enhance viral release:
vpu
vpu ultimately acts to:
reduce cell surface CD4 expression & enhances viral release
vpu and nef are both important:
HIV accessory factors
LTRs
Long terminal repeats
acts as a promoter element for RNA polymerase to begin transcription and also as a terminator element for the stopping of transcription:
Long terminal repeats
Upstream LTR acts as the:
transcriptional promotor
Downstream LTR acts as the:
transcriptional terminator
Promotor responds to host cell cell signals and can also be relatively dormant, creating the ___ that is an important characteristic of HIV
latent state
What state is characteristic of HIV infection?
Latent state
HIV can enter through: (3)
- microabrasians on mucosal surfaces
- needle punctures (IV drug users)
- intact mucosal surfaces
HIV may enter as: (2)
- part of an infected cell (macrophage, lymphocyte & spermatozoa)
- free virus
Describe the viral replication that occurs during initial infection:
The burst of viral replication
During the chronic phase of HIV infection, following the burst of viral replication that occurs during the initial infection, what is continuing to occur?
HIV replication (at slow rate)
What populations of cells are responsible for viral latency?
- long-lived cell populations (macrophages)
- infected resting CD4 lymphocytes
Greater than 99% of viral replication occurs during:
the initial phase
What populations of cells are responsible for greater than 99% of viral replication?
- uninfected activated CD4 lymphocytes
- productively infected CD4 lymphocytes
Neurological dysfunction seen in the later stages of AIDS:
AIDS dementia
How much viral replication is taking place during the latent stage of HIV infection?
Less than 1%
The initial contact of HIV is with:
macrophage lineage cells
After the initial contact of HIV with macrophage lineage cells, they infect/stick to ___ and then transport to the ____ where they will come in contact with ____.
dendritic cells; lymph node; CD4 T cells
DTH:
Delayed-Type Hypersensitivity (Type 4 hypersensitivity)
Important for controlling fungal an intracellular pathogens (bacterial & viral); mediated by CD4 T-cells:
DTH
DTH is mediated by:
CD4 T cells
HIV causes ___ & ___ infection of CD4 T cells
lytic and latent
In addition to HIV causing lytic and latent infection of CD4 T cells, it causes persistent infection of cells of the ___ family and disrupts ____.
monocyte macrophage; neurons
Loss of T-cell function results in:
- severe systemic opportunistic infections
- Kaposi’s sarcoma
- Lymphoma
Although not fully understood, what is though to be the basis of the neurological symptoms caused by HIV?
- possibly due to viral infection of neurons
- possibly due to the release of substances of other cells that promote inflammation of the brain
P24 is a :
viral capsid protein
What is the criterion for AIDS?
Less than 200 CD4 T-cells/mm^3
Patients with higher CD4 T cells than the criterion for AIDs may still be considered to have AIDS if:
If they display AIDS indicator conditions
What follow the initial mononucleosis-like symptoms of HIV infection?
long clinical latency period
The progressive decrease in the number of CD4 T cells, even during the latency period, allows:
opportunistic infections to occur
The stages of HIV disease are defined by the:
- CD4 T cell levels
- Occurrence of opportunistic infections
Due to the loss of CD4 T-cells resulting in AIDs, a patient will be at risk for opportunistic infections such as:
- candidiasis (bronchi, trachea, lungs, esophagus
- kaposi’s sarcoma
- mycobacterium infections
- pneumocystis
HIV transmission occurs by:
direct exposure of person’s blood stream to body fluid containing virus
HIV is found in the ____, ____, or ____ of someone who is infected with the virus
blood, semen, vaginal fluid
HIV is NOT transmitted via:
casual contact
There is a risk for healthcare workers to become infected with HIV via a needle stick however:
less than 1% of exposures show seroconversion
Progressive destruction of CD4+ T cells leading to the collapse of immune system:
AIDS
What type of disease is also associated with AIDS?
central nervous system disease (Specifically dementia)
What cancer is related to AIDS and what is it caused by?
Kaposi’s sarcoma; caused by human herpesvirus 8
Treatment of AIDS involves:
antiviral agents
The antiviral agents that are used to treat AIDS include:
- nucleoside analogue reverse transcriptase inhibitors
- nucleoside RT inhibitors
- protease inhibitors
- fusion-penetration inhibitors
The target of fusion-penetration inhibitors is:
gp41
This study included a recombinant virus assay that was used to characterize ____ directed at circulating autologous HIV in plasma
neutralizing antibody responses
In the study: most patients with primary HIV infection rapidly generated:
significant neutralizing antibody responses to early viruses (0-39 months)
In the study: How does the virus overcome the significant neutralizing antibody response mounted toward early viruses (0-39 months)?
plasma virus continually and rapidly evolved to escape neutralization
In the study: neutralizing antibody extra a level of ___that has been under appreciated based on earlier, less comprehensive characterizations
selective pressure
In the study: the data argues that _____ account for the extensive variation in the envelope gene that is observed in early months after primary HIV infection
neutralizing antibody responses
artificial virions containing altered envelope proteins:
psuedovirions
In the study: the enveloped proteins (gp41 & gp120) come from viral envelope genes amplified from:
patient serum samples
In the study: The HIV DNA on the plasmid created lacks the ___, which had been replaced with __.
envelope gene (env); luciferase
In the study: The replacement of env with luciferase allowed for HIV env genes from patient samples to be used for creation of:
HIV virions
In the study, the env genes are replaced with luciferase and instead expressed from:
a second plasmid in the cells
In the study, the env genes are replaced with luciferase and instead expressed from a second plasmid in the cells and because the virions contain separately supplied env proteins they are considered:
psuedovirions
In the study, the luciferase present within HIV is used to detect ___ by the pseudovirions produced
subsequent infection
In the study, if cells become infected they will express ___, which is easily detected using ____.
luciferase; light-based assay
defined as the reciprocal of the dilution of plasma that produces 50% inhibition of virus replication:
titer
When the virals samples were challenged from various months with plasma samples containing antibodies from the various months after infection, what they found was: (For month zero)
Month zero plasma did NOT neutralize month zero virus
When the virals samples were challenged from various months with plasma samples containing antibodies from the various months after infection, what they found was– comparing month 12 plasma to month 0 virus:
The month 12 plasma (once diluted) was able to neutralize the virus
Why is the plasma antibodies always behind compared to the virus?
the virus that is not susceptible to the antibodies becomes the dominant viral population in the patient
Other human retroviruses include:
Human T-cell lymphotropic viruses (HTLVs -I, -II, -III, - IV)
What human T-cell lymphotropic virus causes adult T-cell leukemia and lymphoma?
HTLV-1
What human T-cell lymphotropic viruses are associated with no known diseases?
HTLV-II, III, IV
