HIV (Exam IV) Flashcards
Describe the 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 surrounding nucleocapsid
- Core conical nucleocapsid
- Envelope glycoproteins
HIV contains ____ 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 & penetration, the use of a coreceptor will:
Dictate the types of cells that will become infected
Initial HIV infection=
M tropic
HIV infection characteristic of cells of macrophage lineage with the use of co-receptor CCR5:
M tropic (initial)
HIV infection characteristic of T cell infection with use of co-recptor 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 co-receptor is engaged what does this allow for?
The virus to become more closely positioned to the cell surface/membrane
After the co-receptor is engaged in an HIV infection, allowing for close proximity of virus to cell surface/membrane what occurs?
A second viral protein gp41 comes in to contact with host cell membrane to promote viral fusion
What would occur in the absence of co-receptor binding by gp120?
Low infectivity of HIV
How was it discovered that a co-receptor is necessary for infectivity of HIV?
A small number of individuals in the population are resistant to HIV infection
Co-receptor interaction during HIV infection is essential for:
gp41 contact & viral fusion with host vell
The individuals in the population who are resistant to HIV infection lack:
The co-receptors
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 nucleocapsid 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 CD4 and to the coreceptor this allows the gp41 protein to be close enough to the host cell membrane to undergo a _______ that causes part of the gp41 protein to engage with both:
Confirmational change; viral envelope & host cell membrane
Following gp41 engagement with both the viral envelope & host cell membrane, a subsequent conformational change pulls the viral envelope & host cell membrane together to _____ & allows the delivery of ____
fuse; the viral nucleocapsid into host cell cytoplasm
In HIV infection, once the nucleocapsid is present within the host cell cytoplasm, the first major step of viral replication involves the use of:
Reverse transcriptase enzyme
What is the first step of action completed by reverse transcriptase in HIV infection?
Takes + stranded RNA & copies it into a DNA strand
What is the second step of action completed by reverse transcriptase in HIV infection?
Takes the DNA strand & copies it into a second complementary strand to create a double stranded DNA complex
What is the first part of HIV genome replication?
Synthesis of viral DNA copy
Reverse transcriptase (RT) synthesizes ____ using viral RNA as the template
One strand of DNA
Reverse transcriptase (RT) 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 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 one of HIV genome replication results in:
a copy of the viral RNA now in double-stranded DNA form
Part two of HIV genome replication is:
Integration of viral DNA copy into host cell genome
In part two of HIV genome replication: integration of viral DNA copy into host cell genome, this step is promoted by:
Viral integrase
Part three of HIV genome replication is:
Transcription of integrated viral DNA copy to create more viral RNA
In part three 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 & viral assembly:
_____ serves as mRNA for translation
____ serves as the viral genome that is packaged into virions
Viral RNA (both)
HIV protein expression & viral assembly:
Viral assembly occurs at the ______
Plasma membrane
HIV protein expression & viral assembly:
Virions acquire their membrane by _____ from the plasma membrane
Budding of nucleocapsids
HIV protein expression & viral assembly:
Translation creates:
Viral polyproteins
HIV protein expression & viral assembly:
Viral polyproteins get cleaved to final mature sizes by:
Viral protease
During an HIV infection, can modulation the host cell & assist the virus in the 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 & enhances viral release:
VPU
VPU ultimately acts to:
- Reduce cell surface CD4 expression
- Enhances viral release
VPU & Nef are both important:
HIV accessory factors
LTRs:
Long terminal repeats
Acts as promoter element for RNA polymerase to begin transcription & also a terminator element to stop the RNA transcription:
Long terminal repeats (LTRs)
The upstream LTR acts as the:
Transcriptional promoter
The downstream LTR acts as the:
Transcriptional terminator
Promoter responds to host 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)
- Microabrasions on mucosal surfaces (sexual contact)
- Needle punctures (IV drug users)
- Intact mucosal surfaces (sexual contact)
HIV may enter as: (2)
- Part of an infected cell (macrophage, lymphocyte, spermatozoa)
- Free virus
Describe the viral replication that occurs during initial infection:
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 very slow rate)
Greater than 99% of viral replication occurs during:
The initial phase
What populations of cells are responsible for viral latency?
- long-lived cell populations (macrophages)
- infected resting CD4 lymphocytes
What population 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 into contact with _____
Dendritic cells; lymph node; CD4 T cells
DTH:
Delayed-type hypersensitivity (Type IV hypersensitivity)
Important for controlling fungal & intracellular pathogens (bacterial & viral); mediated by CD4 T cells:
Delayed-type hypersensitivity (DTH)
DTH is mediated by:
CD4 T cells
HIV causes ____ & _____ infection of CD4 T cells
Lytic & latent
In addition to HIV causing lytic & latent infection of CD4 T cells, it causes persistent infection of cells of the ________ family and disrupts ____
monocyte-macrophage family; neurons
Loss of T cell function due to HIV infection leads to:
- Severe systemic opportunistic infections
- Kaposi’s sarcoma
- Lymphoma
Although not fully understood, what is thought 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 by other cells that promote inflammation in 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:
They display AIDs indicator conditions
What follows 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 in HIV disease are defined by:
- CD4 T cell level
- Occurrence of opportunistic diseases
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 sarcoma
- Mycobacterium infections
- Pneumocystis
Transmission of HIV occurs by:
Direct exposure of person’s bloodstream to body fluid contain 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 health care 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 specific 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 in AIDs treatment:
gp41
The study included a recombinant virus sassy 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 responses mounted towards early viruses (0-39 months)?
Plasma virus continually & rapidly evolved to escape neutralization
In the study:
The neutralizing antibodies exert a level of _____ that has been underappreciated, 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 following primary HIV infection
Neutralizing antibody responses
Artificial virions containing altered envelope proteins:
Psuedovirions
In the study, the envelope 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 has been replaced with _____
envelope gene (env); luciferase
In the study, the replacement of env gene with luciferase allows 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 & because the virions contain separately supplied env proteins they are considered:
Pseudovirions
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 viral samples were challenged from various months with plasma samples containing antibodies from the various months after infect what they found was:
- for month zero
Month zero plasma did NOT neutralize month zero virus
When the viral samples were challenged from various months with plasma samples containing antibodies from the various months after infect what they found was:
-Comparing month 12 plasma to month zero virus
The month 12 plasma (once diluted) was able to neutralize virus by 50% inhibition
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 & lymphoma?
HTLV-I
What human T cell lymphotropic viruses are associated with no known diseases?
HTLV-II, -III, -IV
