Information From Robbins (Hiv/aids)

Front 1

What is AIDS characterized by?

Back 1

Infection
Depletion of CD4+ T lymphocytes
Immunosuppression that leads to secondary neoplasms, opportunistic infections, and neurologic manifestations.

Front 2

What are the three major routes of HIV infection?

Back 2

Sexual contact (men who have sex with men is the largest group of infected persons)
Parenteral inoculation
Passage of virus from infected mother to newborns

Front 3

What are two sexually transmitted diseases that are cofactors for HIV?

Back 3

Gonorrhea and chlamydia
(they increases the seminal fluid content of inflammatory cells which presumably carry HIV)

Front 4

What is the major cause of pediatric AIDS?

Back 4

Mother to infant vertical transmission

Front 5

What are the three routes involved with mother-to-infant transmission of HIV?

Back 5

1. In utero (MOST)
2. Intrapartum (during delivery) = MOST
3. Breastmilk

Front 6

What is the more common strain of HIV among people in the US, Europe, and Central Africa?

Back 6

HIV-1

Front 7

Which HIV strain is more common in West Africa?

Back 7

HIV-2

Front 8

What four things does the virus core of HIV contain?

Back 8

1. Major capsid protein p24
2. Nucleocapsid protein p7/p9
3. TWO copies of genomic RNA
4. Three viral enzymes (protease, reverse transcriptase, and integrase)

Front 9

What is the most readily detected viral antigen and the target for antibodies used to diagnose HIV infection in blood screening?

Back 9

p24 (part of the capsid)

Front 10

What are the three standard retroviral genes?

Back 10

Gag, pol, and env
Code for various viral proteins

Front 11

What is the high variability of the HIV genome due to?\
Where is most of the variation at?

Back 11

Low fidelity of viral polymerase
Envelope glycoproteins

Front 12

What are the two groups of HIV based on genome analysis and which one is most common?

Back 12

M (major) and O (outlier)
M is broken down into A-J with B being the most common in the US and Western Europe

Front 13

What are the two major targets of HIV infection?

Back 13

The immune system and the CNS

Front 14

What does HIV require for entry into cells?

Back 14

The CD4 molecule (a high affinity receptor for the virus)

Front 15

What else must bind to facilitate cell entry?

Back 15

gp120 to coreceptors

Front 16

Describe the fusion process of HIV.

Back 16

HIV gp120 binds to CD4 initially, conformational change that allows gp120 to bind to either CXCR4 (on T cells) or CCR5 (macrophages), gp41 then undergoes a conformational change that allows it to insert into the target membrane.

Front 17

What are the two stains of HIV and what do they bind to? When are they present?

Back 17

R5 which binds to CCR5 expressed on monocytes AND T cells (90% of HIV)
X4 which binds to CXCR4 (expressed ONLY on T cells)

R5 evolves into X4 over the course of the infection

Front 18

Why are some patients resistant to developing AIDS?

Back 18

Defective CCR5 receptor

Front 19

HIV can infect resting T cells, but what is the initiation of proviral DNA transcription caused by?

Back 19

Exposure to antigens or cytokines

Front 20

Why is there a significant drop in T cells in HIV infection during the initial acute phase?

Back 20

Initial infection of T cells is in the mucosal lymphoid tissue (a large reservoir of T cells), causes cell lysis and a sharp drop in T cell count

Front 21

Where is the site of viral replication in the initial acute phase? Where does primary infection occur?

Back 21

Lymph nodes
--Blood and mucosa

Front 22

Where is the virus replicating and destroying cells in the chronic phase of the disease?

Back 22

Lymph nodes and the SPLEEN

Front 23

What is the major mechanism of loss of CD4+ T cells in HIV infection?

Back 23

Lytic HIV infection of the cells
Cell death during viral replication and production of virions

Front 24

What are three mechanisms of cell death that can result from chronic activation of CD4+ T cells?

Back 24

Viral replication of infected cells (cytopathic death)
Activation of uninfected cells (apoptosis)
Expression of HIV peptides in cells that causes death by virus specific CTLs

Front 25

Why is there a selective loss of memory CD4+ T cells early in the course of the disease?

Back 25

Higher expression of CCR5 in this subset and abundance of these cells in the mucosal tissues.

Front 26

What is the "vicious cycle" of the HIV viral mechanism?

Back 26

Decreased helper T cell function leads to increased production of inflammatory cytokines, which stimulates more HIV production followed by infection and loss of additional CD4+ T cells.

Front 27

What are the roles of macrophages?

Back 27

The "gatekeepers of HIV infection" = viral reservoirs and factories
Infected early and hold on to the virus for longer periods that T cells without dying. Can transport the virus to a number of sites throughout the body (particularly the nervous system).

Front 28

Why do you see high levels of B cells in HIV infection?

Back 28

--polyclonal B cell activation
--infections with CMV or EBV
--gp41 can promote B cell growth
--infected macrophages release IL-6 which enhances B cell proliferation
--BUT, the antibodies cannot be mounted against newly encountered antigen (defective)

Front 29

What is brain HIV almost exclusively and why?

Back 29

R5 stain because it was transported there by macrophages (CCR5).

Front 30

What is the major cause of death among AIDS patients?

Back 30

Opportunistic infections