HIV Infection Requires Accomplice – So Called B-cells supply a Molecule Aiding in AIDS Infection of T-cells

HIV Infection Requires Accomplice – So Called B-cells supply a Molecule Aiding in AIDS Infection of T-cells

Researchers in Pittsburg say that the HIV infection of T cells requires activation of a molecule on the surface of B cells. They consider this another pathway that the virus uses to attack the immune system.

Dr. Charles R. Rinaldo said "The research supports a new role for B cells in the development and spread of HIV between cells, with important implications for future studies and drug development efforts that focus on reservoirs of HIV in cells other than T cells." Rinaldo is professor and chairman of the department of infectious diseases and microbiology at Pitt's Graduate School of Public Health (GSPH) and the study's senior author.

Since HIV replicates and thrives in the T-cells of the immune system, most of the drugs being tested in clinical trials focus on these cells. HIV hijacks T cells by binding to a cell membrane molecule called CD4 and to either or both of two other receptors, from which the two strains of HIV, X4 and C5, take their names. After that the virus is able to move into the cells and take command of the cell.

This new pathway discovery is an impotent first step in developing a treatment. While the B cells do not become infected, they “play a pivotal role as an accomplice in HIV's takeover of T cells.”

According to the research to be reported by Giovanna Rappocciolo, Ph.D., research assistant professor of infectious diseases and microbiology at GSPH, laboratory studies provide evidence of DC-SIGN in subsets of B cells from both healthy subjects and HIV infected individuals and indicate DC-SIGN is both a point of entry for HIV and necessary for T cell infection.

B cells were isolated from blood samples obtained in 33 healthy subjects and 20 adult patients with HIV from the Multi-center AIDS Cohort Study (MACS). Researchers found about 8 percent of these cells expressed DC-SIGN.

In one set of studies involving cells from the healthy subjects, the team activated DC-SIGN using two molecules that T cells typically engage in their communication with B cells. Once activated, the DC-SIGN B cells were placed in a culture with T cells and a small amount of virus. Within 24 hours, HIV had begun invading the T cells, yet the B cells were spared. Although they did not become infected, B cells nonetheless harbored virus that was transmissible to T cells for up to two days. HIV had little effect on the T cells when B cells were not present in the culture. Pre-treating the B cells with a molecule that blocks DC-SIGN before culturing them with both T cells and HIV was a deterrent against T cell infection as well, further proof that to invade T cells, HIV requires DC-SIGN to be expressed on B cells.

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