Human Immunodeficiency Virus (HIV) - Virology - The Biology Notes

What is HIV?

HIV stands for ‘human immunodeficiency virus’. It weakens a person’s immune system by destroying important cells that fight against disease and infection.

• HIV is a member of the genus Lentivirus, part of the family Retroviridae.
• It is the causative agent of AIDS.

AIDS is a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive.

Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.

Etiology

HIV is a member of the genus Lentivirus, part of the family Retroviridae. Lentivirus has many morphologies and biological properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period.

Image Source: The Native Antigen Company

Structure and genome

• HIV is different in structure from other retroviruses.
• It is roughly spherical with a diameter of about 120 nm, around 60 times smaller than a red blood cell.

It is composed of two copies of positive-sense single-stranded RNA that codes for the virus’s nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein.

The single-stranded RNA is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as :

1. Reverse transcriptase,
2. Proteases,
3. Ribonuclease
4. Integrase

Epidemiology and Occurrence

Mainly found in AFRICAN jungle. The first outbreak was studied in the 1970s.

Two hypotheses are there to explain its spread and these are  :

1. Hunting hypothesis
2. Polio vaccine hypothesis

• Mainly it causes AIDS in immunocompromised persons.
• First described in United State in 1981 as a new disease entity.
• 35 million people worldwide are living with AIDS.
• In 2009 1.8 million people died of AIDS. And that 2.6 million new infections with HIV occurred.
• According to UNAIDS estimates, about 97,000 people were living with HIV in Pakistan at the end of 2009.

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How Is HIV Transmitted?

• Most commonly, people get or transmit HIV through sexual behaviors and needle or syringe use.
• Only certain body fluid blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, and breast milk from a person who has HIV can transmit HIV.
• Having anal or vaginal sex with someone who has HIV.
• Through sharing personal products and utensils sometimes.

What Is the main target for HIV?

HIV infects vital cells in the human immune system, such as

• Helper T cells (specifically CD4+ T cells),
• Macrophages, and Dendritic cells.

Therefore it weakens the immune system and leads to other opportunistic infections

Entry to the cell

Mechanism of viral entry:

1. Initial interaction between gp120 and CD4.
2. Conformational change in gp120 allows for secondary interaction with CCR5.
3. The distal tips of gp41 are inserted into the cellular membrane.
4. gp41 undergoes significant conformational change; folding in half and forming coiled-coils. This process pulls the viral and cellular membranes together, fusing them.

The HIV virion enters macrophages and CD4+ T cells by the adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the target cell membrane and the release of the HIV capsid into the cell.

Uncoating and release

Then the viral uncoating occurs leads to the release of proteins/enzymes and viral RNA into the host cells.

Replication and transcription

• First of all the Reverse transcriptase enzyme convert RNA into c DNA.
• Then replication of this c DNA into double-stranded DNA occurs.
• This dsDNA then enters into the nucleus of host cells via nucleo pores along with integrase enzyme.
• Integrase enzymes act as molecular scissors that cut the host DNA at the specific sequence and helps in the attachment OR integration of viral secondary DNA into the host DNA strand.
• It is then transcribed into viral m RNA with the help of RNA polymerase and released into the cytoplasm where the ribosome transcribes it into new envelope proteins and viral genome.
• The surface proteins move out to the cell and other proteins collection near to cell surface occurs.

Assembly and release

Then protease enzyme cut the polynucleotide into specific proteins and then assembly of these viral proteins take place. After that, the new viral progeny released and ready to attack other cells

Pathogenesis of HIV Infection

• Infection with HIV starts without symptoms or ill-feeling and is accompanied by slight changes in the immune system. This stage spans up to three months after infection.
• During primary infection, although individuals may look healthy, the virus is actively replicating in the lymph nodes and bloodstream of infected individuals. As a result, the immune system may get slowly damaged by the burst of viral load in their bodies.
• Symptomatic stage of disease indicates the late phase of HIV disease (AIDS) where individuals may be susceptible to other opportunistic infections such as infections with :

1. Mycobacterium avium,
2. Mycobacterium tuberculosis,
3. Pneumocystis carinii,
4. CMV,
5. toxoplasmosis and
6. candidiasis.

It is agreed that infected individuals develop an AIDS status when their plasma HIV load is high and the CD4+ T count is less than 200 mm3.

Diagnosis

Count of CD4+ T cells is determined. If it is less then 200 mm3 then it is positive for AIDS.

Drug resistance. Some strains of HIV are resistant to medications. This test helps your doctor determine if your specific form of the virus has resistance and guides treatment decisions.

The primary tests for diagnosing HIV and AIDs include:

ELISA Test — ELISA, which stands for enzyme-linked immunosorbent assay, is used to detect HIV infection. If an ELISA test is positive, the Western blot test is usually administered to confirm the diagnosis

Saliva Tests — A cotton pad is used to obtain saliva from the inside of your cheek. The pad is placed in a vial and submitted to a laboratory for testing. Results are available in three days. Positive results should be confirmed with a blood test.

Viral Load Test — This test measures the amount of HIV in your blood. Generally, it’s used to monitor treatment progress or detect early HIV infection. Three technologies measure HIV viral load in the blood: reverse transcription-polymerase chain reaction (RT-PCR), branched DNA (bDNA) and nucleic acid sequence-based amplification assay (NASBA).