Sunday 21 December 2014

The Basic Science of HIV/AIDS

Steve Sipes and Michael Sugarman What is HIV?

Steve Sipes and Michael Sugarman

What is HIV?

The Human Immunodeficiency Virus (HIV) is a retrovirus (defined below) that causes Acquired Immuno Deficiency Syndrome (AIDS) in humans. In brief, HIV works by depleting the immune system of specific types of white blood cells, leaving the body unable to fight off infections. HIV, like all viruses, requires a living host to survive and replicate.

What is AIDS?

AIDS is the clinical diagnosis given to HIV-infected patients that also display AIDS-related illnesses and/or have a low white blood cell count. A low white blood cell count as well as verification of the presence of HIV is considered the most accurate method in diagnosing AIDS, because a person may not display AIDS-related symptoms for quite some time after contracting HIV.

How is HIV transmitted?

HIV transmission from person to person occurs via the direct contact with HIV infected blood entering your body through your anus, mouth, tip of your penis, small cuts in your skin or vagina. Bodily fluids that contain high blood content, such as semen, breast milk and vaginal secretions can directly transmit HIV to another person. Transmissions can arise from such activities as accidental syringe sticks, the sharing of needles (including unsterile tattooing and piercings), childbirth (mothers passing on HIV to the unborn child within the womb) and unprotected sex (including oral and anal sex). It is important to point out that HIV cannot be transmitted through other bodily fluids, (even though minute traces of blood might exist) such as saliva from kissing, tears, sweat, urine, or insect bites. Infection does not also occur from skin to skin contact such as touching, holding or hugging a person infected with HIV.

What does HIV look like?

The main components of HIV consist of an outer protein-lipid envelope and the viral core (see the figure below) which contains the viral genome and proteins. This envelope, composed of the viral env glycoprotein (sugar-modified protein) and other proteins and lipids derived from the host white cell, surrounds the viral core. The viral core is a cone- or bullet-shaped capsid consisting of a p17 protein coat surrounding a p24 protein envelope. Inside the protein envelope are two identical single-stranded RNA molecules and three enzymes, reverse transcriptase, integrase and protease, required for replication of the virus. HIV is approximately 120 nanometers (one nanometer is a billionth of a meter) in diameter, as compared to a Red Blood Cell which is roughly 6,000 nanometers in diameter. HIV has just nine genes compared to approximately 25,000 in a human.

What is a retrovirus?

A retrovirus is a virus that has a single-stranded RNA ( not DNA ) genome (nearly all organisms, including humans, have a double-stranded DNA genome) and relies on an enzyme it carries, called a reverse transcriptase, to make a double-stranded DNA copy of its RNA genome. This DNA is integrated into the host cell's genome via another viral enzyme called integrase. After being integrated, the retroviral DNA is referred to as a provirus. If a provirus has been integrated into germ-line cells (eggs or sperm), it is passed on to the following generation (the offspring). This process has been occurring for many thousands of years in humans and these retroviral sequences now account for approximately 8% of the human genome!

While transcription (making RNA using DNA as a starting template) was once thought to only occur in one direction from DNA to RNA, it was discovered that the reverse, making DNA from RNA, is also possible. This was hypothesized (predicted) by Howard Temin in 1962 while studying retroviruses and proven independently by both Temin and David Baltimore in 1970, It is called reverse transcription because of this ability to ‘reverse' the transcription process by copying an RNA into DNA before more RNA can be made. The reverse transcriptase lacks the usual ability of DNA replicases to correct mistakes ( i.e. proofreading) made during the copying process. This error-prone process results in a uncorrected mutations in subsequent viral genomes. HIV's reverse transcriptase is significantly more error-prone than those most retroviruses, enabling this virus to become rapidly resistant to antiviral pharmaceuticals and to alter the structure of its env protein which impedes the development of an effective HIV-vaccine.

How does HIV infect a host cell?

HIV infection of a host cell begins when a protein sticking out from the virus recognizes and binds to the CD4 receptor present on a host CD4 T cell (one of several types of cells of the immune system). This results in the fusion of the viral envelope surrounding the virus capsid with the host cell membrane. Following this fusion, the capsid containing the viral RNA and enzymes enter the host cell's cytoplasm. Once inside the cell, the reverse transcriptase converts the viral RNA to DNA. This DNA is transported to the nucleus where it is incorporated into the human chromosomal DNA by the integrase.

Interestingly, an HIV provirus may lie dormant within a human cell for years. Once the cell becomes activated, it treats HIV genes in much the same way as human genes. First, it copies them into messenger RNAs (mRNA) using human enzymes. Then, this mRNA is transported out of the nucleus and is used as a blueprint for producing new HIV proteins and enzymes. Among the mRNA strands produced (transcribed) by the cell are complete copies of the HIV genome. These gather together with newly made HIV proteins to form new HIV particles. The accumulation of these particles is then pushed outside the cell, taking part of the cell membrane with it to use as a new viral membrane.

What are the initial symptoms of an HIV infection?

Although i nfection of T cells with HIV is immediate after exposure, time until presentation of initial symptoms of AIDS varies greatly, depending on the individual and their immune system. As such, HIV diagnosis cannot be determined solely by observation of an AIDS-related symptom. Multiple symptoms combined may be indicative of HIV infection, but could also be attributed to other immunodeficiency illnesses. Because of the general nature of symptoms, a person must be tested specifically for HIV to conclusively determine their HIV status. This is done by either looking for antibodies directed against HIV or isolating the virus from a patient's blood sample. Once infection has occurred, the body tries to fight off the virus by producing antibodies that will attack the virus. The presence of these antibodies is the indicator that HIV infection has occurred. Another method at later stages of infection is determining the presence and quantity (viral load) of the virus directly. Usually, testing for the antibodies is sufficient to confirm infection.

Possible warning signs of an HIV infection may include the following:

  • rapid weight loss
  • dry cough
  • recurring fever or profuse night sweats
  • profound and unexplained fatigue
  • swollen lymph glands in the armpits, groin, or neck
  • diarrhea that lasts for more than a week
  • white spots or unusual blemishes on the tongue, in the mouth, or in the throat
  • pneumonia
  • red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids
  • memory loss, depression, and other neurological disorders

This list was taken from the U.S. National Center Disease Control & Prevention website, available at


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