HIV Uses Trojan Horse Method to Infect Cells

HIV-Infected T Cell
T-cell lymphocyte immune cell infected with HIV (yellow). Credit: National Institute of Allergy and Infectious Diseases (NIAID)

HIV Uses Trojan Horse Method to Infect Cells

Like all viruses, HIV is not able to reproduce or express its genes without the help of a living cell. First, the virus must be able to successfully infect a ​cell. To do so, HIV uses a veil of human ​proteins in a Trojan horse manner to infect immune cells. To go from cell to cell, HIV is packaged in an "envelope" or capsid made from viral proteins and proteins from human cell membranes.

Like the ebola virus, HIV relies on proteins from human cell membranes to gain entrance into a cell. In fact, Johns Hopkins scientists have identified 25 human proteins that have been incorporated into the HIV-1 virus and aid its ability to infect other body cells. Once inside a cell, HIV uses the cell's ribosomes and other components to make viral proteins and to replicate. When new virus particles are formed, they emerge from the infected cell cloaked in a membrane and proteins from the infected cell. This helps the virus particles avoid immune system detection.

What Is HIV?

HIV is the virus that causes the disease known as acquired immunodeficiency syndrome, or AIDS. HIV destroys cells of the immune system, making an individual infected with the virus less equipped to fight off infection. According to the Centers for Disease Control (CDC), this virus may be transmitted when infected blood, semen, or vaginal secretions come in contact with an uninfected person's broken skin or mucous membranes.

There are two types of HIV, HIV-1 and HIV-2. HIV-1 infections have mostly occurred in the United States and Europe, while HIV-2 infections are more prominent in West Africa.

How HIV Destroys Immune Cells

While HIV may infect different cells throughout the body, it attacks white blood cells called T cell lymphocytes and macrophages in particular.

HIV destroys T cells by triggering a signal that results in T cell death. When HIV replicates within a cell, viral genes get inserted into the genes of the host cell. Once HIV integrates its genes into T cell DNA, an enzyme (DNA-PK) uncharacteristically sets off a sequence that leads to the death of the T cell. The virus thereby destroys the cells that play a major role in the body's defense against infectious agents. Unlike T cell infection, HIV infection of macrophages is less likely to lead to macrophage cell death. As a result, infected macrophages produce HIV particles for a longer period of time. Since macrophages are found in every organ system, they can transport the virus to various sites in the body. HIV-infected macrophages may also destroy T cells by releasing toxins that cause nearby T cells to undergo apoptosis or programmed cell death.

Engineering HIV-Resistant Cells

Scientists are attempting to develop new methods for fighting HIV and AIDS. Stanford University School of Medicine researchers have genetically engineered T cells to be resistant to HIV infection. They accomplished this by inserting HIV-resistant genes into the T-cell genome. These genes successfully blocked entry of the virus into the altered T cells.

According to researcher Matthew Porteus, "We inactivated one of the receptors that HIV uses to gain entry and added new genes to protect against HIV, so we have multiple layers of protection -- what we call stacking. We can use this strategy to make cells that are resistant to both major types of HIV." If it is shown that this approach to treating HIV infection could be used as a new type of gene therapy, this method could potentially replace current drug therapy treatment. This type of gene therapy would not cure HIV infection but would provide a source of resistant T cells that could stabilize the immune system and prevent the development of AIDS.

Sources:

  • NIH/National Institute of Allergy and Infectious Diseases. "Scientists discover how HIV kills immune cells; Findings have implications for HIV treatment." ScienceDaily. ScienceDaily, 5 June 2013. (www.sciencedaily.com/releases/2013/06/130605144435.htm).
  • Herbein G. and Kumar A. The macrophage: a therapeutic target in HIV-1 infection. Molecular and Cellular Therapies. Published 2 April 2014. (http://www.molcelltherapies.com/content/2/1/10).
  • Stanford University Medical Center. "Immune cells engineered in lab to resist HIV infection, study shows." ScienceDaily. ScienceDaily, 22 January 2013. (http://www.sciencedaily.com/releases/2013/01/130122101903.htm).