HIV-1 Flashcards
HIV-1 genome
Two copies of positive polarity RNA
HIV-1 capsid symmetry
icosahedral
HIV envelope?
Yes, includes gp120 and gp41
gp120
interact with CD4 to attach to T cells
CD4 =
TCR coreceptor for recognizing antigen
CXCR4 and CCR5
cell homing, interact with growth factors
gp41
injection of viral contents into host cell
New HIV cases annually
US = 44,000 Worldwide = 2 million
People living with HIV-1 infection
US = 1.2 million Worldwide = 36.9 million
Minnesota HIV
7 dx per 100,000
vs. Louisiana = 36.6
vs. Montana = 1.9
gag
capsid proteins (p24 et al)
pol
reverse transcriptase, protease, integrase
env
envelope glycoproteins gp120 and gp41
LTRs
3’ and 5’
integration sites, bind host transcription factors NF-kB, Sp1, TBP
The HIV-1 genome is ____ and _____, with genes encoded on _________.
The HIV-1 genome is small and compact, with genes encoded on multiple overlapping reading frames.
The products of the gag, pol and env genes make up ________
the functional HIV-1 infectious particle
Gene products, eg. tat, rev and nef, encode ______
transcriptional regulators
The binding of the infectious HIV-1 particle to the host cell is initiated by ___________
interaction between gp120 and CD4.
_________ is also required to initiate infection.
Interaction between a host chemokine receptor (CXCR4 or CCR5) and gp41
_________ can occupy HIV-1 binding sites on ______ and block infection.
Stromal derived factor (SDF-1) on CXCR4
________ may be associated with natural resistance to HIV-1 infection.
SDF-1 polymorphisms
SDF-1 normal function
to bind CXCR4 on lymphocytes and direct their homing to tissues.
HIV steps in infection cycle
gp120 bind CD4, gp41 bind chemokine receptor –> fusion and insertion into cell
RNA via RT –> dsDNA
integrase inserts into cellular DNA = provirus
Expression of viral genes to make viral proteins and viral genomes
Proteolytic processing of viral proteins
Assembly of viral particles and budding from host cell
normal binding of CXCR4
Stromal derived factor -1 (SDF-1) normally functions to bind CXCR4 on lymphocytes and direct their homing to tissues.
HIV pathology, binding of CXCR4
HIV-1 infected T cells (provirus) express env proteins on their cell surface. Binding of env to CXCR4 induces autophagy. This is a major cause of CD4+ T cell loss in HIV-1 infection.
Major cause of CD4+ T cell loss in HIV-1 infection
HIV-1 infected T cells (provirus) express env proteins on their cell surface. Binding of env to CXCR4 induces autophagy.
Bystander
IL-2 response
Th1, activates CTLs (CD8+ T cells)
IL-4, 5, 6 response
Th2, activates B cells to become plasma cells
Th1 cells
IL-2, IFN-g, IL-3, TNF-a, TNF-b, GM-CSF induce CD8+ CTLs B cell IgG antibody Macrophage activation (M1) Inhibit Th2
Th2 cells
IL-3, IL-4, IL-5, IL-6, IL-10, IL-13 Inhibition of Th1 Eosinophils Mast cells, basophils B cell IgM, G, A, and E antibodies
CD4+ T cells mediate immune responses against
viruses, bacteria, fungi, parasites and cancer.
Opportunistic Infections
Viral:
Kaposi sarcoma virus (KSV, HHV-8)
Cytomegalovirus (CMV, HHV-4)
Fungal:
Candida
Protozoa:
Cryptococcus
Pneumocystis (?)
p24 is a
capsid protein encoded by gag
spikes right away, detectable before p24 antibodies, then goes down as antibody increases, and then grows again
To diagnose HIV
ELISA, confirmed by western blot
To monitor patients with HIV
CD4+ T cell enumeration by flow cytometry
Polymerase chain reaction: viral RNA or DNA
Goal of therapy for patients with HIV
reduce level of circulating virus
A 53 year old female is HIV-1 positive with a CD4 count of 130 cells/uL. She has Kaposi sarcoma lesions on her arms and torso which first appeared one month ago.What is the most likely cause of her Kaposi sarcoma?
Inefficient activation of CD8+ T cells
A patient’s blood was collected and labeled with fluorescent antibodies against CD3, CD4 and CD8. In the dot plot, only CD3 positive cells are shown. What cells are represented by the dots in the upper right quadrant?
Immature T cells
What is the structure of a nucleoside
No phosphate (phosphate = nucleotide) Base, ribose sugar
A 19 year old male had unprotected sex with a person who was HIV positive. The next day, he asked his family physician whether he had contracted HIV. What screening test would detect HIV the soonest after exposure? CD4+ T cell enumeration Indirect ELISA for anti-p24 antibodies PCR for viral mRNA RT-PCR for viral DNA Sandwich ELISA for p24 antigen Western blot
Sandwich ELISA (direct) for p24 antigen p24 antigen spikes soon after infection as the virus disseminates systemically
A 25 year old HIV-1 positive male is on a combination antiretroviral drug regimen, but his compliance has been sporadic. His CD4 count has recently declined to 250 cells/ul. His physician is developing a new treatment plan.In this patient, if 1 in 105 viral particles are resistant to ziduvudine and 1 in 106 viral particles are resistant to lopinavir, what is the probability that a viral particle will be resistant to both zidovudine and lopinavir?
1 in 10^11
A 38 year old male immigrant from Cap-Haitien, Haiti presents with a dry cough that has persisted for three weeks. He is confirmed to be HIV-1 positive, with levels of CD4 cells and viral RNA consistent with AIDS. Microscopic analysis of induced sputum show P. jirovecii sporozoites.The first line treatment for his pneumonia targets. . .
Trimethoprim - Sulfamethoxazole
sequential steps in tetrahydrofolic acid synthesis.
An 18 year old female is infected with HIV-1 and is being treated with multiple drugs including ritonavir. What is ritonavir’s mechanism of antiviral action?
Protease inhibitor
A 42 year old HIV-1 positive female is showing disease progression despite a HIV-1 treatment regimen consisting of zidovudine, abacavir and atazavavir with ritonavir boosting. Testing indicates the presence of abacavir resistant virus.Which drug should be included in a new drug regimen? abacavir didanosine emtricitabine lamivudine nevirapine
Zidovudine = AZT (NRTI) Abacavir = NRTI
Atazanavir/Ritnoavir = Protease inhibitors
Abacavir resistance --> also get zidovudine resistance and other NRTI resistance so no: abacavir didanosine emtricitabine lamivudine
Use nevirapine = NNRTI (no cross resistancE)
