Study appearing in PLoS ONE also reports that macrophages act as a site of recombination of the viral makeup.
Researchers say that in diseased cells like cancer cells that are also infected with HIV, almost all the virus is packed into macrophages. What’s more, up to half of those macrophages were hybrids, formed when pieces of genetic material from several parent HIV viruses combined to form new strains.
The higher frequency of recombinant virus in diseased tissues is likely because macrophages multiply as a result of an inflammatory response, the scientists explain. They conclude that HIV-infected macrophages might be implicated in tumor-producing mechanisms.
The team also believes that viral load in HIV patients never goes down to zero when treated with T-cell targeting drugs because of the viral load that still exists in macrophages. Unlike T cells, macrophages live for several months, all the while being re-infected with multiple viruses of different genetic makeup, they explain.
“The study points to macrophages as a site of recombination in active disease,” says neurobiologist Kenneth C. Williams, Ph.D., a Boston College associate professor who was reportedly not involved in the study.
“Most people who look at viral sequences assume that evolution of the virus is linear,” Dr. Williams adds. “In the real world that doesn’t happen. Large parts of the virus are swapped in and out.” He notes that the current findings overturn the old way of trying to match virus sequence with pathology.
The study, which was published in PLoS ONE, set out to see if HIV populations that infect abnormal tissues are different from those that infect normal ones. They also wanted to figure out whether particular strains are associated with certain types of illness.
The team used frozen post-autopsy tissue samples, pathology results, and advanced computational techniques. They analyzed 780 HIV sequences from 53 normal and abnormal tissues collected from seven patients who had died between 1995 and 2003 from various AIDS-related conditions including HIV-associated dementia, non-Hodgkin’s lymphoma, and generalized infections throughout the body. Four patients had been treated with HAART at or near the time of death.
The researchers compared brain and lymphoma tissues, which had heavy concentrations of macrophages, with lymphoid tissues such as from the spleen and lymph nodes that had a mix of HIV-infected macrophages and T cells.
The analyses revealed great diversity in the HIV strains present, with different tissues having hybrid viruses made up of slightly different sets of genes. A high frequency of such recombinant viruses was also found in tissues generally associated with disease processes, such as the meninges, spleen, and lymph nodes.
Some Pathogens Found to Use TLR–Induced Enzyme in Macrophages to Suppress Immunity (Nov. 3, 2008)
Researchers Reveal How HIV Protein Thwarts Immune System (Sept. 26, 2008)
Cryptococcus Yeast Eludes Detection by Using Macrophages to Travel through the Body (Sep. 9, 2008)
Proteins Linked to HIV-Resistance Identified in Kenyan Sex Workers (Sept. 2, 2008)