HIV-1

Question 1

HIV-1 genome

Answer 1

Two copies of positive polarity RNA

Question 2

HIV-1 capsid symmetry

Answer 2

icosahedral

Question 3

HIV envelope?

Answer 3

Yes, includes gp120 and gp41

Question 4

gp120

Answer 4

interact with CD4 to attach to T cells

Question 5

CD4 =

Answer 5

TCR coreceptor for recognizing antigen

Question 6

CXCR4 and CCR5

Answer 6

cell homing, interact with growth factors

Question 7

gp41

Answer 7

injection of viral contents into host cell

Question 8

New HIV cases annually

Answer 8

US = 44,000
Worldwide = 2 million

Question 9

People living with HIV-1 infection

Answer 9

US = 1.2 million
Worldwide = 36.9 million

Question 10

Minnesota HIV

Answer 10

7 dx per 100,000

vs. Louisiana = 36.6
vs. Montana = 1.9

Question 11

gag

Answer 11

capsid proteins (p24 et al)

Question 12

pol

Answer 12

reverse transcriptase, protease, integrase

Question 13

env

Answer 13

envelope glycoproteins gp120 and gp41

Question 14

LTRs

Answer 14

3’ and 5’

integration sites, bind host transcription factors NF-kB, Sp1, TBP

Question 15

The HIV-1 genome is ____ and _____, with genes encoded on _________.

Answer 15

The HIV-1 genome is small and compact, with genes encoded on multiple overlapping reading frames.

Question 16

The products of the gag, pol and env genes make up ________

Answer 16

the functional HIV-1 infectious particle

Question 17

Gene products, eg. tat, rev and nef, encode ______

Answer 17

transcriptional regulators

Question 18

The binding of the infectious HIV-1 particle to the host cell is initiated by ___________

Answer 18

interaction between gp120 and CD4.

Question 19

_________ is also required to initiate infection.

Answer 19

Interaction between a host chemokine receptor (CXCR4 or CCR5) and gp41

Question 20

_________ can occupy HIV-1 binding sites on ______ and block infection.

Answer 20

Stromal derived factor (SDF-1) on CXCR4

Question 21

________ may be associated with natural resistance to HIV-1 infection.

Answer 21

SDF-1 polymorphisms

Question 22

SDF-1 normal function

Answer 22

to bind CXCR4 on lymphocytes and direct their homing to tissues.

Question 23

HIV steps in infection cycle

Answer 23

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

Question 24

normal binding of CXCR4

Answer 24

Stromal derived factor -1 (SDF-1) normally functions to bind CXCR4 on lymphocytes and direct their homing to tissues.

Question 25

HIV pathology, binding of CXCR4

Answer 25

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.

Question 26

Major cause of CD4+ T cell loss in HIV-1 infection

Answer 26

HIV-1 infected T cells (provirus) express env proteins on their cell surface. Binding of env to CXCR4 induces autophagy. Bystander

Question 27

IL-2 response

Answer 27

Th1, activates CTLs (CD8+ T cells)

Question 28

IL-4, 5, 6 response

Answer 28

Th2, activates B cells to become plasma cells

Question 29

Th1 cells

Answer 29

``` IL-2, IFN-g, IL-3, TNF-a, TNF-b, GM-CSF induce CD8+ CTLs B cell IgG antibody Macrophage activation (M1) Inhibit Th2 ```

Question 30

Th2 cells

Answer 30

``` 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 ```

Question 31

CD4+ T cells mediate immune responses against

Answer 31

viruses, bacteria, fungi, parasites and cancer.

Question 32

Opportunistic Infections

Answer 32

Viral: Kaposi sarcoma virus (KSV, HHV-8) Cytomegalovirus (CMV, HHV-4) Fungal: Candida Protozoa: Cryptococcus Pneumocystis (?)

Question 33

p24 is a

Answer 33

capsid protein encoded by gag spikes right away, detectable before p24 antibodies, then goes down as antibody increases, and then grows again

Question 34

To diagnose HIV

Answer 34

ELISA, confirmed by western blot

Question 35

To monitor patients with HIV

Answer 35

CD4+ T cell enumeration by flow cytometry | Polymerase chain reaction: viral RNA or DNA

Question 36

Goal of therapy for patients with HIV

Answer 36

reduce level of circulating virus

Question 37

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?

Answer 37

Inefficient activation of CD8+ T cells

Question 38

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?

Answer 38

Immature T cells

Question 39

What is the structure of a nucleoside

Answer 39

``` No phosphate (phosphate = nucleotide) Base, ribose sugar ```

Question 40

``` 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 ```

Answer 40

``` Sandwich ELISA (direct) for p24 antigen p24 antigen spikes soon after infection as the virus disseminates systemically ```

Question 41

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?

Answer 41

1 in 10^11

Question 42

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. . .

Answer 42

Trimethoprim - Sulfamethoxazole sequential steps in tetrahydrofolic acid synthesis.

Question 43

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?

Answer 43

Protease inhibitor

Question 44

``` 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 ```

Answer 44

``` 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)