S1B4 - HIV Flashcards

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1
Q
A
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2
Q

How can the general time course of untreated HIV infection be divided?

A

The time course of untreated HIV infection can be divided into four stages:

  1. Stage 1 is the acute stage which is characterized by wide dissemination of virus and seeding of lymphoid organs that can present as flu-like symptoms. During this time CD4 counts are decreasing with an acute rise in HIV RNA copies.
  2. Stage 2 is clinical latency and includes mild symptoms, which may include mucocutaneous manifestations and recurrent respiratory tract infections. CD4 count drops below 500.
  3. Stage 3 is the appearance of advanced symptoms such has unexplained chronic diarrhea and severe bacterial infections. CD4 counts usually drop below 350.
  4. Stage 4 or AIDS is characterized by many opportunistic diseases with CD4 counts less than 200.
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3
Q

Describe the process by which HIV inserts itself into the host genome.

A

Once inside a cell, viral reverse transcriptase converts viral RNA to double-stranded DNA. This double-stranded DNA is inserted into the host cell genome by integrase, another viral enzyme.

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4
Q

Describe the basic virology of HIV (capsid, enveloped/noneveloped, genetic material).

A

Human Immunodeficiency Virus (HIV) is a complex and conical capsid, enveloped, diploid positive sense single-stranded RNA (ssRNA) lentivirus (a slow type of retrovirus). The 2 RNA strands are identical.

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5
Q

What is the function of the accessory protein Nef in the context of HIV?

A

Nef is a cytoplasmic accessory protein that enhances viral replication through down-regulation of CD4 and MHC-I expression.

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6
Q

Name 3 possible mechanisms by which the CD4+ cells decrease with HIV infection.

A

The decrease in CD4 cells are due to several mechanisms:

  • Cell lysis due to budding
  • CD8 cells attacking HIV infected cells
  • Multinucleated giant cell formation, where syncytia formation occurs due to the interaction of gp120 in triggering the exposure of gp41 that favors insertion into the cellular membrane that allows for cellular membrane linkage
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7
Q

What is the surface protein that facilitates fusion of viral envelope to the target cell membrane in HIV?

A

gp41 mediates viral-cell fusion and syncytia formation.

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8
Q

What is the role of RT-PCR in the management of HIV?

A

Viral loads can be determined from RT-PCR, which can help monitor the efficacy of drug therapy.

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9
Q

Which immune cells does HIV primarily target? What cellular receptors are targeted?

A

HIV infects CD4 T lymphocytes and macrophages by binding to CD4, CCR5 (on macrophages in early infection), and CXCR4 (on T-cells in late infection).

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10
Q

What is the function of the regulatory protein Rev in the context of HIV?

A

Rev is a regulatory protein that regulates viral RNA transport of unspliced viral transcripts out of the nucleus. Rev and Tat are essential for HIV replication.

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11
Q

Once the proviral HIV DNA is inserted into the host genome what are the enzyme/proteins made from the following genes? - env? - gag? - pol?

A

Following insertion of proviral DNA into the host genome, the host cell transcription and translation machinery can be exploited to generate the viral polyproteins:

  • env (gp120 and gp41)
  • gag (p24 and p7)
  • pol (reverse transcriptase, aspartate protease, integrase)
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12
Q

What is HAART used for and what does the regimen usually consist of?

A

Highly active antiretroviral therapy (HAART) is a combination of antiretroviral drugs to control HIV infection. Current treatment regimen consists of three drugs: 2 NRTIs that serve as the “backbone,” and a protease inhibitor, nNRTI, or integrase inhibitor that serves as the “base.”

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13
Q

How can HIV be transmitted?

A

Transmission of HIV can occur through transfer of bodily fluids such as blood, semen, breast milk, and vaginal fluids from events such as sexual activity, IV drug abuse, birth, and blood transfusions.

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14
Q

What is the function of the regulatory protein Tat in the context of HIV?

A

Tat is a regulatory protein that transcriptionally activates other viral genes. Tat and Rev are essential for HIV replication.

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15
Q

What is p24 protein’s clinical significance in relation to HIV?

A

p24 is the capsid protein and is also located in the core. Antibodies to p24 can act as an early serologic marker of infection.

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16
Q

What are the two criteria for diagnosing AIDS?

A

The criteria for AIDS is CD4 count less than 200, or confirmed HIV positivity with AIDS-defining opportunistic infections such as Pneumocystis pneumonia or Candida esophagitis.

17
Q

What HIV proteins are being detected in ELISA and Western blot?

A

Diagnosis of HIV has traditionally been made initially with ELISA, and positive results are confirmed with Western blot. ELISA and Western blot can detect antibodies to gp41, gp120, or p24 depending on the antibodies used in the tests. Western blot is considered positive if the patient demonstrates the presence of antibodies to at least 2 of the 3 important HIV antigens.

18
Q

What GHRH analog can be given to treat HIV-associated lipodystrophy?

A

HIV-associated lipodystrophy can be treated by the GHRH analog tesamorelin.

19
Q

What is the primary serological test for the diagnosis of HIV? What is the confirmatory serological test?

A

Diagnosis of HIV is made via detection of HIV p24 antigen and HIV antibodies, and positive tests are confirmed via HIV-1/HIV-2 antibody differentiation immunoassays.

20
Q

Homozygous mutations of which cellular receptor confers immunity to HIV infection? What effect does heterozygous mutations of the same effector have on HIV infection?

A

CCR5 mutations can confer protection against HIV. Homozygous mutations have been shown to give immunity against HIV, and heterozygous mutations have been shown to have a higher resistance to HIV infection.

21
Q

What is the major surface antigen of HIV that interacts with the CD4 receptors?

A

gp120 (major surface antigen) binds CD4, CXCR4 on T cells, and CCR5 on macrophages.