Cholesterol Metabolism Linked to Lack of HIV-1 Progression
HIV-1 trans infection not seen in nonprogressors; can be restored by cholesterol reconstitution
WEDNESDAY, April 30, 2014 (HealthDay News) -- Cholesterol metabolism seems to be associated with a lack of HIV-1 trans infection, seen in HIV-1 infected nonprogressors (NPs), according to a study published online April 29 in mBio.
Noting that HIV-1 infected NPs inhibit disease progression without antiretroviral therapy, Giovanna Rappocciolo, Ph.D., from the University of Pittsburgh, and colleagues examined mechanisms for this resistance to disease progression.
The researchers found that two types of professional antigen presenting cells (APCs) (dendritic cells and B lymphocytes) from NPs were unable to mediate HIV-1 trans infection of CD4+ T cells, while HIV-1 trans infection was effectively mediated by APCs from HIV-1 infected progressors (PRs) and HIV-1 seronegatives (SNs). Similarly efficient direct cis infection of T cells with HIV-1 was seen among NPs, PRs, and SNs. There was a link between lack of HIV-1 trans infection in NPs with lower cholesterol levels; and in APCs, but not T cells, there was an increase in the levels of the ATP-binding cassette, reverse cholesterol transporter ABCA1 in NPs. Reconstitution of cholesterol and inhibiting ABCA1 by messenger RNA interference restored trans infection mediated by APCs from NPs.
"The present study demonstrates a new mechanism wherein enhanced lipid metabolism in APCs results in remarkable control of HIV-1 trans infection that directly relates to lack of HIV-1 disease progression," the authors write.