HIV Found to Replicate Outside CD4 Cells; Discovery Gives Insight Into HIV-related Dementia
In an intriguing new study published last week in PLoS Pathogens, researchers discovered the first solid proof that HIV can replicate itself in cell types other than CD4 cells. The finding potentially opens an important window on our understanding of HIV-related dementia.
The study's senior author, Ronald Swanstrom, Ph.D., and his coauthors examined the cerebrospinal fluid (CSF) of people diagnosed with HIV-associated dementia. In some of the patients, they found two genetically distinct types of HIV, which they believe could contribute to HIV-associated neurological problems.
One of the two HIV variants found in CSF reproduces in CD4 cells, as does the virus growing in the blood. But the other type does not. It infects and replicates in macrophages, another white immune cell that engulfs and digests foreign material, including bacteria.
"This is the first time that anyone has demonstrated active replication of HIV virus in a cell type other than [CD4] cells," Swanstrom said in the press release.
Researchers have known for many years that macrophages trap HIV -- macrophage means "big eaters"; their role is to engulf harmful pathogens and diseased cells in tissues of the body. Once a macrophage encases a pathogen like HIV, the macrophage displays pieces of the virus on its membranes and produces chemicals, known as cytokines, to alert other cells of the immune system to the presence of the pathogen in bodily tissues.
CD4s are among the immune system cells to respond to the macrophage's plea for help. For years, researchers believed that the only way HIV can escape the macrophages is by being passed on to the CD4 cells, where the virus can begin replicating. The new research by Swanstrom's group suggests that HIV can reproduce in macrophages without any help from CD4 cells.
They also compared the rates at which HIV disappeared from blood versus CSF after starting antiretroviral treatment. The time it takes for something to decrease by half, or half-life, for HIV in the blood is short, generally one to two days. But interestingly, for half of the study participants, HIV in the CSF disappeared much more slowly, having a half-life of several weeks to a month, suggesting the virus was hiding in a different type of cell that lived longer.
This new information helps us further understand how HIV affects the central nervous system, and it may influence decisions when it comes to starting meds -- not only when to start, but also what to start with, since some HIV medications get into the CSF more easily than others. The researchers will continue their work on a new study that will look for biomarkers in CSF that help predict cognitive progression for HIV-positive individuals on treatment.
But this latest study reveals yet another one of HIV's tricks. Sooner or later, we'll find them all.