Immediately after the discovery of HIV, scientists rushed to describe the virus and to identify the process by which it infects cells and ultimately leads to immune system failure.   In thousands of research reports researchers have slowly, painstakingly elucidated this information.      Future prospects for a "cure" hinge on understanding how the virus works in all of its exquisite detail.   Summarizing the mountain of complex information already developed on the subject in a format easily understood by a non-scientists is-- in itself-- a daunting task.

What follows is a very sketchy overview of the process for a reader with a non-technical interest in the subject.   Wherever possible, we have tried to highlight steps in the sequence exploited by researchers in devising treatment strategies.    Please scroll down to find links providing greater depth of information and images explaining the process further.

About the Human Immunodeficiency Virus (HIV)

We start with some basic information about the virus.

HIV is a Retrovirus

HIV belongs to a class of viruses called retroviruses, which have genes composed of ribonucleic acid (RNA) molecules.   In contrast, the genes of humans and almost all other organisms are made of a related molecule, deoxyribonucleic acid (DNA) .   
Like all viruses, HIV can replicate only inside cells-- commandeering the cell's machinery to reproduce.   However, only HIV and other retroviruses use an enzyme called reverse transcriptase to convert their RNA into DNA, which can be incorporated into the host cell's genes.   Since only retroviruses use this enzyme (i.e., and it is not used by the host cell), treatment strategies have focused heavily on this enzyme.   

Structure of HIV

The viral envelope.    HIV has a diameter of 1/10,000 of a millimeter and is spherical in shape.   The outer coat of the virus, known as the viral envelope, is composed of two layers of fatty molecules called lipids.    These lipids actually come from the membrane of a human cell when a newly formed virus particle buds from the cell.   

Embedded in the viral envelope are proteins from the host cell together with copies of a complex HIV protein that protrudes from the envelope surface.   This Envelope protein, known as Env, consists of a cap and a stem that anchors the structure in the viral envelope.   Much of the research to develop a vaccine against HIV has focused on portion of this complex envelope protein.   

The viral core (or capsid).   Within the envelope of a mature HIV particle is a bullet-shaped core made of 2000 copies of another viral protein (p24.)   The core surrounds two single strands of HIV RNA, each of which has a copy of the virus's nine genes.   

The core of HIV also includes another protein (p7), the HIV nucleocapsid protein; and three enzymes that carry out later steps in the virus's life cycle: reverse transcriptase, integrase and protease.   

Steps in Viral Replication
The replication of HIV within the body occurs in a predictable sequence of nine steps:

0. Attachment/Entry: The virus attaches to a particular type of white blood cells (CD4+ T Cells)
1. Reverse Transcription and DNA Synthesis: Viral RNA is transcribed to DNA and replicated
2. Transport to Nucleus: The new DNA moves into the nucleus
3. Integration: The new DNA is integrated with the host cell's DNA
4. Viral Transcription: New copies of the viral RNA are produced.
5. Viral Protein Synthesis: Viral proteins are produced.
6. Assembly of Virus: Components of the virus gather near the cell membrane and form by a 'pinching' action of the membrane.
7. Release of Virus: The new virus "buds" off from the host cell
8. Maturation: Long strands of viral RNA and protein are cleaved into smaller segments by proteases.

• Click here for more information on these steps.
  

How HIV Works
The healthy body's immune system fights-off infection with a combination of cellular and chemical responses.   White blood cells of various types play a large role in the immune response to infection by microbial agents (e.g., viruses and bacteria).   

HIV infection is so incredibly devastating because it renders the infected body virtually unable to protect itself from infection.    HIV works by attacking key elements in the normal cellular immune response-- leaving the host subject to infection from a wide array of infectious agents.   

Most notably, crucial white blood cells cells called CD4+ T cells are disabled and killed during the infection.   These cells, sometimes called "T-helper cells," play the central role in the normal immune response, signalling other cells in the immune system to perform their special functions.   Without these "helper cells", other parts of the immune system fail to function.   

Often, when someone is said to have "died from AIDS", in reality, the true cause of death might have been pneumonia, tuberculosis, or some other disease which took hold because the HIV-infected immune system could not combat it.   

Early Events in HIV Infection
Once it enters the body, HIV infects a large number of CD4+ T-cells and replicates rapidly.   During this acute or primary phase of infection, the blood contains many viral particles that spread throughout the body, seeding various organs, particularly the lymphoid organs.   Lymphoid organs include the lymph nodes, spleen, tonsils and adenoids.

During the acute phase of infection, the number of CD4+ T cells in the bloodstream decreases by 20 to 40 percent.   Scientists do not yet know whether these cells are killed by HIV or if they leave the blood and go to the lymphoid organs in preparation to mount an immune response.

Two to four weeks after exposure to the virus, up to 70 percent of HIV-infected persons suffer flu-like symptoms related to the acute infection.   The patient's immune system fights back with killer T cells (CD8+ T cells) and B-cell-produced antibodies, which dramatically reduce HIV levels.   A patient's CD4+ T cell count may rebound to 80 to 90 percent of its original level.   A person then may remain free of HIV-related symptoms for years despite continuous replication of HIV in the lymphoid organs seeded during the acute phase of infection.

Course of HIV Infection
In western countries, the median time from infection with HIV to the development of AIDS has been approximately 10 to 12 years -- but that varies widely.    Approximately 10 percent of HIV-infected people in many studies have progressed to AIDS within two to three years after infection.    About one in 20 individuals maintains stable CD4+ T cell counts and shows no symptoms even after 12 or more years.

Factors such as age or genetic differences among individuals, the amount of virus in the original inoculum (material transmitted during the infectious contact), the individual strain of virus, and infection with other diseases may influence the rate and severity of disease progression.   Drugs that fight the infections associated with AIDS (e.g., Pneumocystis carinii pneumonia) have improved and prolonged the lives of HIV-infected people by preventing or treating these conditions.

Although HIV-infected individuals often exhibit an extended period of clinical latency with little evidence of disease, the virus is never truly latent (dormant).   Even early in disease, HIV actively replicates within the lymph nodes and related organs, where large amounts of virus become trapped.

New anti-HIV drug combinations which generally include a protease inhibitor taken with two reverse transcriptase inhibitors can reduce a person's "viral burden" to very low levels and in many cases delay the progression of HIV disease for prolonged periods.   However, antiretroviral regimens have yet to completely and permanently suppress the virus in HIV-infected people.   

The information above was extracted from a Fact Sheet produced by the National Institute of Allergy and Infectious Diseases (NIAID) , the branch of the National Institutes of Health responsible for combatting infectious diseases.

For more information, please visit the following links:

• The complete NIAID Fact Sheet with diagrams
• The Life Cycle of HIV with photomicrographs
• A Slide Show on Prospects for Treating HIV with info & graphics on basic virology
  
• The Basic Science and Pathogenesis of HIV An On-line Textbook. Very technical
  

Many of these resources and more can be found at AEGIS.COM, a very comprehensive source of HIV information targeted to the lay-person.