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the virus

HIV can replicate itself as many as a trillion times a day.

What is HIV?

The human immunodeficiency virus (HIV) is part of a class of viruses known as retroviruses. Most viruses carry a double-stranded piece of DNA, which they insert into host cells in order to reproduce. A retrovirus contains just a single-stranded piece of RNA, which is converted into DNA once it's inside a host cell.

RNA-to-DNA conversion is a sloppy process during which many mistakes -- scientists call them mutations -- are made. Some mutations don't matter at all; some actually make the virus less effective or kill it completely; and some mutations help the virus find ways around the body's immune response or any drugs that might target the virus.

How do you get HIV?

Peter Piot

Executive Director of UNAIDS Dr. Peter Piot on how HIV is transmitted (0:29)

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Unlike a flu virus, which can live for hours outside a human body and can be easily spread through the air or other surfaces, HIV can't live outside a body for more than a few minutes, nor can it be killed by soap nor is it easily transmissible. It can only be passed through blood or through contact between mucosal surfaces. The only bodily fluids that contain HIV in significant amounts are semen, vaginal fluid, and breast milk. HIV cannot be spread through contact with saliva, tears or sweat.

The primary ways HIV spreads are:

  • Sex (either vaginal or anal)
  • Blood transfusions
  • Sharing of contaminated needles
  • From mother to child at birth
  • Breastfeeding

In rare cases, HIV can also be spread through oral sex, especially where the throat is already inflamed.

How does the virus invade a cell?

HIV Viron Diagram
David Baltimore

Nobel Prize-winning virologist Dr. David Baltimore on how HIV hides from the immune system (1:27)

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After HIV enters the body, it hunts down and penetrates the CD4 cell, which functions as the immune system's quarterback: It tells the other cells what they need to do to rid the body of an invader. HIV hijacks the CD4 cell and uses the cell's machinery to make new virions, or virus particles. Here's how:

After penetrating a CD4 cell, the virus goes to work turning it into an HIV factory.

HIV disguises itself behind a layer of sugars, which makes it appear harmless (although some cells do recognize and destroy HIV particles). Because immune system cells are constantly circulating in and out of the lymph organs, the HIV-infected cell will soon carry the virus straight to the stronghold of the lymphatic system, where CD4 cells are most abundant. Once there, HIV begins replicating and infecting CD4 cells very quickly. It replicates itself billions of times each day.

Imagine HIV as a sphere with spiky proteins all over its surface. In order to infect a CD4 cell, one of those proteins, known as gp120, fits together with a receptor protein, CCR4, on the CD4 cell's surface, like a key fits into a lock. A second protein, called gp41, then locks onto a second receptor protein, CCR5. Once both connections are made, the virus can penetrate the outer wall of the cell and insert its viral proteins and RNA.

After penetrating a CD4 cell, the virus goes to work turning it into an HIV factory. An enzyme called reverse transcriptase transcribes the viral RNA into DNA. Then another enzyme, known as integrase, cuts apart the cell's own DNA, and inserts the viral DNA. The virus has become a provirus -- a viral cell that can lie dormant for years until it's activated. Once the cell is activated, its DNA tells the cell to produce more copies of the RNA and other proteins needed to make new HIV virions. After the copies are made, they gather at the cell's surface and form buds before finally disconnecting from the host cell. Once they're free, an enzyme called protease cuts the new proteins and RNA into small, usable pieces. The new virions are now mature, and ready to do battle with the body.

Why are some people immune?

In the mid-1990s, after scientists discovered that HIV needs to bind to two receptor proteins, Dr. Stephen O'Brien, chief of the Laboratory of Genomic Diversity at the National Cancer Institute, identified a small number of people who, despite repeated exposures to HIV, had not been infected. He found that these people had a mutated form of one of HIV's receptor proteins, the CCR5 protein on the surface of the CD4 cell. This genetic abnormality doesn't do any harm, and it gives those who have it immunity from HIV.

But how did this particular mutation develop? Testing the DNA of direct descendants of villagers from the British town of Eyam, which went into voluntary quarantine after being infected by the plague in 1665, Dr. O'Brien discovered that those who survived the black death all had the CCR5 mutation. To confirm his theory, he tested people from all different backgrounds for the mutation. Native Americans, Africans, and Asians did not have the mutation at all, but about 14 percent of the descendants of Eyam did, as did people descended from other areas hit hard by the plague.

O'Brien's discovery led to a breakthrough in HIV treatment: the third class of anti-HIV drugs developed, called fusion inhibitors, which bind to the CCR5 protein to protect CD4 cells from HIV. [Read more on Dr. O'Brien's discovery.]

How does HIV destroy the body?

Cleve Jones

Activist Cleve Jones on finding out he was HIV positive (2:08)

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Almost immediately upon infection, the immune system recognizes that it is under attack. Many people experience flu-like symptoms, sometimes with a rash, two to three weeks after being infected. This is the body reacting to the invading HIV and mounting a terrific immune response, producing up to a billion helper and killer T-cells a day. At this point, there is enough virus in the blood that HIV can be diagnosed through a blood test.

Because the virus infects CD4 cells, stimulating the immune system means activating infected CD4 cells, which then produce more viruses. Those viruses in turn go out and infect more of the newly created CD4 cells.

Because they have such large armies, the body and HIV can battle each other for up to 10 years or longer. During this time, the HIV-infected person will feel totally healthy. But since the virus is incredibly active, the person can spread HIV to anyone with whom he or she exchanges bodily fluids, such as blood, vaginal fluid, semen or breast milk.

Phill Wilson

AIDS activist Phill Wilson on watching his lover die from AIDS (1:34)

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Eventually HIV gains the upper hand and begins to kill off more CD4 cells than the body can produce. Without the CD4 cells, the B-cells and killer T-cells lack instruction about where to go and what to look for, and the body's immune response becomes less and less effective.

When is a person diagnosed with AIDS?

AIDS is diagnosed by measuring how many CD4 cells are found in a cubic millimeter of blood.

  • A normal adult has between 400 and 1600 CD4 cells per cubic millimeter of blood.
  • A person in the nonsymptomatic stage of HIV has between 500 and 600 cells per cubic millimeter of blood.
  • Every time the CD4 count drops by 100, a person's relative risk of acquiring AIDS doubles.

The most common marker of an individual's progression to AIDS is a CD4 count of 200 or fewer cells per cubic millimeter of blood. By that point, the immune system essentially ceases to function, leaving the person very vulnerable to any kind of infection. [Read more about CD4 counts.]

Why do some people with HIV never progress to AIDS?

Researchers have found that 1 percent of HIV-positive people are "nonprogressors": they seem to be able to fight HIV so successfully that it doesn't progress to AIDS. These people maintain stable and very low levels of the virus in their blood. Many have been healthy and HIV positive for more than a decade without receiving any treatment at all, while some get sick but experience a very slow progression of the disease.

So far, scientists have found several explanations: Some of the nonprogressors have a particular gene pattern that allows their body to identify and kill HIV virions more frequently than most people. Others seem to have CD4 cells that are more resistant to being infected by HIV, while still others have a strain of HIV that's missing viral protein R (Vpr), which reduces its ability to infect CD4 cells. Each type of long-term nonprogressor offers clues for the future of HIV treatment, but as yet of there have been no major breakthroughs.

When an HIV-positive person has both a low CD4 count and what doctors call an "AIDS-defining illness" or "opportunistic infection," that person has AIDS. Early symptoms of worsening HIV infection include night sweats, fatigue, weight loss, and hugely swollen lymph nodes. Some of the most common life-threatening, AIDS-defining diseases are:

  • Kaposi's sarcoma (KS) -- a skin cancer characterized by purple lesions. Before AIDS, KS was usually seen in older men of Eastern European descent. This once highly visible sign of the illness is less common now than it was during the '80s and early '90s because doctors have learned to prevent or control it.
  • Pneumocystis carinii pneumonia (PCP)-- a rare form of pneumonia seen in people with suppressed immune systems. Symptoms include extreme shortness of breath; treatment requires heavy doses of antibiotics combined with oxygen therapy. PCP is currently a common infection in people with AIDS, and many suffer several bouts of it before dying.
  • Candidiasis, or thrush -- an explosive fungus growth that can occur in the mouth, throat, windpipe or on the skin. It appears most frequently in men as a white coating of the mouth and causes burning, a bad taste and lack of appetite. Women can also get it in the mouth, but often one of the first warning signs for women is a chronic vaginal candidiasis that does not respond to treatment. The fungus naturally lives in the body in small quantities, but without a healthy immune system to keep it in check, it can run rampant. In rare cases, candidiasis spreads throughout the body and becomes a life-threatening condition.
  • Toxoplasmosis -- a parasite that infects the brain and can cause brain damage and blindness. In the United States alone, up to 60 million people are thought to be infected with the parasite, but the immune system normally keeps it under control. Before AIDS, toxoplasmosis was considered a minor danger for pregnant women.
  • Cytomegalovirus (CMV) -- a member of the herpes family of viruses and one of the leading causes of blindness and death in people with AIDS. It is another virus that is common in adults, but is normally held in check by a healthy immune system. CMV can infect any part of the body, but in people with AIDS, it generally attacks the eye.

Doctors can treat each of these conditions and most other opportunistic infections, but when HIV has destroyed the immune system, these diseases can take hold with fatal results. In the late stages of AIDS, HIV can begin attacking other cells besides the immune system's. Scientists don't entirely understand HIV's impact on the nervous system, but frequently, individuals with AIDS begin to experience dementia, problems with balance, and an inability to move their legs and arms. HIV can also attack a person's internal organs.

  • Related Links
  • The Body: HIV Basics
    The Body is a comprehensive Web site about HIV and AIDS. Geared toward those who are infected, or think they might be, this page starts with the basics, outlines prevalent myths that still exist about HIV, and offers a quiz to test your knowledge of HIV/AIDS.
  • NOVA: Surviving AIDS
    More about how the CCR5 gene was discovered and how genetic "outliers" might still give valuable clues to fighting HIV.
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posted may 30, 2006

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