Compendium Review: AIDS Supplement

Opportunistic Infections (Frolich PowerPoint)

Who is affected? (Frolich PowerPoint)

HIV Life Cycle

Structure of HIV

Virus Replication
I. Origin of and Prevalence of HIV
II. Phases of an HIV Infection
III. HIV Structure and Life Cycle

I. Origin of and Prevalence of HIV
A. HIV: Human Immunodeficiency Virus: The virus that causes AIDS.
B. AIDS: Acquired Immunodeficiency Syndrome
C. HIV infects and kills cells of the immune system, specifically helper T cells and macrophages. As the number of T cells decline, the body can't fight an infection, and the person becomes ill with various diseases.
D. Opportunistic Infection: One that has the opportunity to occur only when the immune system is really weakened.
E. History: Originated in Africa. First cases may have been in the 1950s. It is speculated that the disease originated in monkeys, and was transmitted to humans when humans ate the primates. 1969: First documented case in the US- a 15 year old boy. The name AIDS was created in 1982, when the disease became understood.
F. Prevalence of HIV: Pandemic, because the disease is prevalent in the entire human population all over the world.
- An estimated 36.3 million adults and 2.3 million children are living with HIV.
- Most people infected with HIV live in developing countries.
- Sub-Saharan Africa and Asia: represents 64% of all people living with HIV.
- Latin America and the Caribbean
- North America, Europe, and Central Asia
- North Africa and the Middle East
- Oceania (Mader 344-345)
II. Phases of an HIV Infection
A. HIV occurs as several subtypes: HIV-1B causes most infections in the US.
- Phases of HIV-1B: 1. Helper T cells and macrophages infected with HIV are called CD4 cells. When these are destroyed, the immune system is significantly impaired. One of the leading causes of AIDS related deaths in the US is Pneumocystis jiroveci pneumonia, while in Africa, it is tuberculosis.
B. 1993: Centers for disease control issued guidelines for the classification of HIV. Three categories / Phases, based on the CD4 T cell count and the history of AIDS-defining illnesses.
1b. Category A: Acute Phase- Asymptomatic: No physical signs.
- Highly infectious.
- CD4 T cell count that has never fallen below 500 cells per mm3. Normal = 800.
- Immune system functions normally.
- In general, it takes about 25 days before there are detectable levels of HIV antibodies in body fluids.
2b. Category B: Chronic Phase
- CD4 count between 499 and 200 cells / mm3.
- One or more symptoms related to an impaired immune system: yeast infections of mouth or vagina, cervical dysplasia, prolonged diarrhea, thick sores on tongue, or shingles, amongst many others.
- Number of HIV particles is on the rise during this phase.
3b. Category C: AIDS- Diagnosis of AIDS occurs.
- CD4 T cell count has fallen below 200 cells / mm3 OR the individual has one or more of the 25 AIDS-defining illnesses.
- Persons with AIDS die from one of the following opportunistic diseases, not from the HIV infection itself:
- Pneumocystis jiroveci pneumonia- fungal infection of lungs.
- Myobacterium tuberculosis: a bacterial infection usually of lymph nodes or
lungs, but can be in other organs.
- Toxoplasmic encephalitis: Protozoan parasitic infection, often seen in brain.
- Kaposi's sarcoma: an unusual cancer of the blood vessels.
- Invasive cervical cancer: Spreads to nearby tissues.
C. Even though there is no cure for AIDS, many people are living longer because of the use of antiretroviral therapy. (Mader 346-347)
III. HIV Structure and Life Cycle
A. Consists of two single-strands of RNA, various proteins, and an envelope, which it takes from its host cell.
B. The virus's genetic material is protected by three protein coats: nucleocapsid, capsid, and the matrix. 1b. Within the matrix, there are three enzymes:
- Reverse transcriptase: Catalyzes reverse transcription, the conversion of the viral RNA to viral DNA.
- Integrase: Catalyzes the integration of viral DNA into the DNA of the host cell.
- Protease: Catalyzes the breakdown of newly synthesized viral polypeptides into functional viral proteins.
C. Protein spikers (Gp120) are found in the envelope of HIV, and are necessary for HIV to gain entry into its target immune cells.
D. HIV is a retrovirus: Uses reverse transcription to convert its RNA into viral DNA.
E. HIV Life Cycle (Reproductive Cycle of Virus)
1e. Attachment: HIV binds to plasma membrane of target cell. Gp120 (spike) binds to a CD4 receptor on surface of helper T cell or macrophage.
2e. Fusion: HIV fuses with plasma membrane; virus enters cell.
3e. Entry: Uncoating: the capsid and protein coats are removed, releasing RNA and viral proteins into cytoplasm of host cell.
4e. Reverse Transcription: Unique to retrovirus. Enzyme called reverse transcriptase catalyzes the conversion of HIV's single-stranded RNA to double-stranded viral DNA.
5e. Integration: Newly synthesized viral DNA , along with integrase, migrates into nucleus of host cell. Host cell's DNA is spliced, and then integrated by viral DNA into host cell's DNA, and HIV is provirus: now a part of cell's genetic material.
6e. Biosynthesis and Cleavage: Normal cell machinery directs the production of more viral RNA
7e. Assembly: Capsid proteins, viral enzymes, and RNA can now be assembled to form new viral particles.
8e. Budding: Virus gets its envelope and envelope marder coded for by viral genetic material.
(Insert HIV Life Cycle picture / Frolich PowerPoint Slide 31)
F. Transmission and Prevention of HIV
1f. Transmitted by sexual contact with an infected person, including vaginal or rectal intercourse and oral / genital contact. Also by needle-sharing among drug users. Also can be transmitted via blood transfusions. (Mader 348-349)
G. Prevention: Blood semen, vaginal fluid, and breast mile are body fluids known to have highest concentration of HIV. Not transmitted through casual contact.
2f. Abstinence
3f. Sex with only one uninfected partner.
4f. Condom use. (Mader 349)
G. Testing and Treatment
1g. HIV test does not test for the virus itself, it tests for the presence of HIV antibodies in the body.
2g. There is now hope, because therapy is available to control HIV replication and keep patients in the chronic phase much longer than before.
3g. Drug Therapy: Highly active antiretroviral therapy us usually able to stop HIV replciation to such an extent that the viral load becomes undetectable. However, if HAART is discontinued, the virus rebounds, so therapy is continued indefinitely.
4g. Vaccines: 2010: hoping to have a vaccine. (Mader 350)