HIV

Question 1

What are the 3 major genes of the HIV genome?

Answer 1

ENV GAG POL Envy gag pol

Question 2

What sequence is at both ends of the HIV genome? What is its function?

Answer 2

On both ends, the LTR sequence. Long terminal repeat. TWO functions 1) Used by the enzyme INTEGRASE to insert the reverse transcribed DNA into the genome. 2) PROMOTER/ENHANCER function to induce viral genome transcription.

Question 3

Function of the ENV gene

Answer 3

codes for the essential Envelope proteins, which then get glycosylated. gp120 and gp41

Question 4

Function of GAG gene

Answer 4

GAG, Group Antigen Genes Capsid p24 protein, which binds the RNA to the capsid Matrix proteins (proteins that lie under the envelope)

Question 5

Function of POL gene

Answer 5

The essential enzymes for making the viral DNA. Protease - cleaves GAG and POL proteins from a common precursor protein after translation. Integrase Reverse Transcriptase

Question 6

What are some other important regulatory and accessory proteins of HIV (6)

Answer 6

rev - Directs splicing away from the accessory proteins and towards the Gag Pol Env proteins. (tat and rev are both alternative splice products of the larger Env precursor protein) tat - TransActivaTor promoter protein nef - Nef nerfs CD4 and MHC 1 protein expression in infected T cells vpu - also inhibits CD4 and MHC1 vpr - essential for nuclear import of HIV-1 and replication in macrophages vif - involved in DNA insertion and inhibition of intracellular antiviral nucleases

Question 7

Methods of transmission

Answer 7

Male-male sex is still #1 mode in the US, Heterosexual sex main mode in Africa, and second mode in the US IV drug use Transplacental Blood transfusions of: whole blood, concentrated red or white blood cells, concentrated clotting factors, or plasma. Not transmitted by concentrated gamma-globulins. Sexual, most likely to transmit to the receiver, because breaks in the anal/vaginal mucosa are more likely than within the penile urethra or skin. The virus is in high concentrations in seminal fluid, vaginal, and cervical secretions It is transmissible by oral sex but at very low rates.

Question 8

What are the viral components that mediate cell invasion? What is the viral receptor and co-receptors?

Answer 8

gp41 and gp120 together make gp160 It binds the CD4 molecule of T helper cells, gp41 is the stalk (inner part in the lipid envelope) and gp120 is the head (outer part) One of the co-receptors is required: CCR5 CXCR4 Macrophages express both the co-receptors which can mediate its entry without CD4.

Question 9

Stages of the HIV infection

Answer 9

1) Acute viral illness. 3-6 weeks after infection Presents like mononucleosis: fever, fatigue, lymphadenopathy, and pharyngitis High level viremia. Lasts for several weeks and then self-resolves 2) Clinical latency with HIV replication in the lymphoid tissue. 2-20 years, usually 8. Minimal viremia, but virus is replicating in the lymphoid tissue. CD4 counts progressively drop. 60/ul/year Skin infections Constitutional symptoms: night sweats, fever, weight loss, widespread lymphadenopathy. 3) AIDS, Immune Deficiency Syndrome. CD4 counts are less than 200. and An AIDS defining infection; Candida esophagitis, Pneumocystis carnii pneumonia, Kaposi-sarcoma, Mycobacterium avium intracellulare disseminated infection, cryptococcus neoformans fungus meningitis, disseminated Herpes Zoster

Question 10

What are the AIDS associated bacterial infections

Answer 10

Mycobacterium tuberculosis Mycobacterium avium intracellulare

Question 11

AIDS associated fungal infections?

Answer 11

PCP, Pneumocystis Jiroveci Pneumonia- The *most* common opportunisitic AIDS infection in the US. Candida esophagitis Cryptococcus neoformans, meningitis Histoplasma capsulatum Coccidioides immitis

Question 12

AIDS associated viral infections

Answer 12

Disseminated herpes zoster

Epstein Barr virus -> Oral Hairy Leukoplakia

B cell lymphoma

CMV esophagitis and retinitis

Question 13

AIDS associated protozoa infections

Answer 13

Toxoplasma gondii - Ring enhancing mass lesions in the brain. Fever, headache Seizures, Focal neurologic deficits.

• Cryptosporidium. parva hominis. Cryptosporidium ph.
• Microsporidia
• Isosspora belli -All three cause chronic diarrhea.

Question 14

AIDS associated Malignancies

Answer 14

Two most common: 1) Kaposi Sarcoma 2) B-Cell lymphoma,

EBV associated often presents as a brain mass

Others at increased risk:

Non-Hodgkins lymphoma

Hodgkins lymphoma

Cervical cancer

Anal intraepithelial neoplasia

Question 15

Prophylactic treatment of AIDS patients:

Answer 15

Trimethoprim and sulfamethoxazole, which prevents both: Pneuomocystis jiroveci Toxoplasma gondii

Azithromycin or Clarithromycin To prevent Mycobacterium Avium-Intercellulare

Gancyclovir or foscarnet to prevent Cytomegalovirus

Acyclovir to prevent Herpes VZV

Candida treated with Nystatin orally, treated systemic with amphotericin B or fluconazole.

Question 16

Diagnostic tests for HIV

Answer 16

ELISA for antibodies against it, but doesn’t work until 3 to 6 weeks after infection b/c body needs to make antibodies. This can take as long as 6 months, therefore multiple tests must be done, also because there is a high rate of false positives.

Rapid HIV tests, also rely on anti HIV antibodies.

Either test must then be confirmed with a Western blot using ENV GAG and POL proteins separated and probed with the patients sera, then visualized with anti-human secondary antibody.

To test earlier than 3 weeks, use a PCR test on blood sample for HIV RNA. PCR must also be used to test infants/neonates of HIV positive mothers for infection, since the mothers antibodies against HIV will be present in the infants blood for some time before/after birth.

Question 17

What are the antiviral treatments used to treat HIV itself?

Answer 17

HAART treatments with combination therapy is essential because HIV is so variable and rapidly mutating.

The most common is triple drug therapy with two NRTIs, and one NNRTI or Protease Inhibitor 1) NRTIs. Nucleotide reverse transcriptase inhibitors. Nucleotide analogs that halt elogation of the nucleotide. Classical example is Zidovudine and Lamivudine. Especially use Zidovudine during pregnancy, labor, and for mothers post-partum. 2) NNRTIs. Non-nucleoside reverse transcriptase inhibitors Elfavirenz 3) Protease inhibtors Saquinavir

CCR5 inhibitors Maraviroc

Entry inhibitors Enfuvirtide

Integrase inhibitors Raltegravir