Navigate Up
UPMC/University of Pittsburgh Schools of the Health Sciences
Senior Manager
Telephone: 412-578-9193 or 412-624-3212

Patients and medical professionals may call 1-800-533-UPMC (8762) for more information.
 

 

UPMC Media Relations

HIV Infection Requires B Cells With Special Protein, University Of Pittsburgh Researchers Report

Study in PLoS Pathogens identifies new pathway that may aid in treating, preventing HIV

PITTSBURGH, July 13, 2006 — HIV infection of T cells requires activation of a molecule on the surface of B cells, a finding that reveals yet another pathway the virus uses in its insidious attack on the immune system, report University of Pittsburgh Graduate School of Public Health (GSPH) and School of Medicine researchers in PLoS Pathogens, an open-access journal published by the Public Library of Science. While preliminary, the research suggests a need for developing a class of antiviral drugs targeted against this molecule and offers an avenue that may prove critical for the prevention of HIV.

Nearly all approved HIV drug regimens and most of those being tested in clinical trials focus on T cells, where HIV replicates and thrives. 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. Once anchored on the membrane, it’s able to slither inside and take command of the cell. The new research identifies an important first step in a new pathway involving B cells that express a protein called DC-SIGN. While these cells themselves do not become infected, they play a pivotal role as an accomplice in HIV’s takeover of T cells.

“We have new insight into how the virus does its damage. The pathway is surprisingly simple, yet it has important implications for future studies and drug development efforts that focus on reservoirs of HIV in cells other than T cells,” said Charles R. Rinaldo, Jr., Ph.D., professor and chairman of the department of infectious diseases and microbiology at Pitt’s GSPH and the study’s senior author.

The researchers report evidence of DC-SIGN in subsets of B cells from both healthy subjects and HIV infected individuals. Laboratory studies of these cells indicate DC-SIGN is 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 Multicenter AIDS Cohort Study (MACS), 10 of whom had suppressed virus due to antiretroviral therapy (ART) and 10 who had never undergone ART. Researchers found about 8 percent of these cells expressed DC-SIGN. The researchers also confirmed their presence in tissue by examining samples from five non-HIV tonsillectomy patients. In tonsils, a lymphoid organ where both T cells and B cells congregate and engage in cross talk, 26 percent of the B 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 invaded the T cells while sparing the B cells. When researchers repeated the experiment without B cells, the HIV had little effect on the T cells alone. Pretreating the B cells with a molecule that blocks DC-SIGN activation 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 expressed on B cells.

DC-SIGN was first identified as a dendritic cell-specific binding site for HIV, but with this study, Dr. Rinaldo and colleagues prove that B cells expressing DC-SIGN also are used by HIV to facilitate infection of T cells.

“As has been observed in DC-SIGN dendritic cells, we suspect the B cells internalize the virus and that the DC-SIGN serves as sort of a bridge HIV uses to reach the surface of T cells,” noted Giovanna Rappocciolo, Ph.D., associate professor of infectious diseases and microbiology at GSPH and the study’s first author.

In addition to Drs. Rinaldo and Rappacciolo, other authors include Paulo Piazza, Ph.D., Craig L. Fuller, Ph.D., Todd A. Reinhart, D.Sc., Simon C. Watkins, Ph.D., David T. Rowe, Ph.D., Mariel Jais and Phalguni Gupta, Ph.D..

The research was supported by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute of the National Institutes of Health.

Note to editors: The study can be found at http://dx.doi.org/10.1371/journal.ppat.0020070 after 8 p.m., EDT, on Thursday, July 13.

©  UPMC | Affiliated with the University of Pittsburgh Schools of the Health Sciences
Supplemental content provided by A.D.A.M. Health Solutions. All rights reserved.

For help in finding a doctor or health service that suits your needs, call the UPMC Referral Service at 412-647-UPMC (8762) or 1-800-533-UPMC (8762). Select option 1.

UPMC is an equal opportunity employer. UPMC policy prohibits discrimination or harassment on the basis of race, color, religion, ancestry, national origin, age, sex, genetics, sexual orientation, marital status, familial status, disability, veteran status, or any other legally protected group status. Further, UPMC will continue to support and promote equal employment opportunity, human dignity, and racial, ethnic, and cultural diversity. This policy applies to admissions, employment, and access to and treatment in UPMC programs and activities. This commitment is made by UPMC in accordance with federal, state, and/or local laws and regulations.

Medical information made available on UPMC.com is not intended to be used as a substitute for professional medical advice, diagnosis, or treatment. You should not rely entirely on this information for your health care needs. Ask your own doctor or health care provider any specific medical questions that you have. Further, UPMC.com is not a tool to be used in the case of an emergency. If an emergency arises, you should seek appropriate emergency medical services.

For UPMC Mercy Patients: As a Catholic hospital, UPMC Mercy abides by the Ethical and Religious Directives for Catholic Health Care Services, as determined by the United States Conference of Catholic Bishops. As such, UPMC Mercy neither endorses nor provides medical practices and/or procedures that contradict the moral teachings of the Roman Catholic Church.

© UPMC
Pittsburgh, PA, USA UPMC.com