Activated CD4+
T cells have been known for some time as especially susceptible to HIV
infection, and that they form the largest reservoir of latently infected cells.
But not all CD4+ T cells contribute equally to the pool of such dormant
infected cells.
Dr.
Asier Sáez-Cirión
amfAR grantees Asier Sáez-Cirión from the Pasteur Institute in Paris, Nicolas Chomont of the
University of Montreal, and other colleagues sought to determine if other
features of subsets of T cells also contribute to their susceptibility to HIV
infection and creation of a latent state.
Writing in the
April issue of Cell Metabolism, they
found that differences in susceptibility to HIV infection matched the level of
metabolism of particular T cell subsets, and that this was true regardless of
their activation profile. Cellular pathways linked to sugar metabolism and
oxidation were particularly relevant. These metabolic distinctions were
maintained in T cell subsets despite their state of activation.
Utilizing T
cells from 6 HIV-positive donors who had maintained undetectable levels of
virus after 3 to more than 16 years of antiretroviral therapy, the researchers showed
that expression of certain genes important in cell metabolism correlated
strongly with susceptibility to HIV infection. Moreover, partial inhibition of
sugar metabolism in the test tube suppressed the susceptibility of these cells to
HIV infection, and blocked amplification of the virus in cells from the
HIV-infected individuals.
The authors
concluded that their results “identify vulnerability in tackling HIV reservoirs.”
These reservoirs are a major impediment to curing HIV, and such metabolic vulnerabilities
may be targeted by new therapies.
Dr. Laurence is amfAR’s senior
scientific consultant.