UA Researchers Find Clues to Why AIDS Progresses More Rapidly in HIV-1 Infected Infants than in Adults

Researchers at The University of Arizona College of Medicine have identified a mechanism that explains the faster progression of AIDS in HIV-1 infected newborns and infants than in adults.

Researchers at The University of Arizona College of Medicine have identified a mechanism that explains the faster progression of AIDS in HIV-1 infected newborns and infants than in adults.

In a study published in the July 17-21 online issue of Proceedings of the National Academy of Sciences (PNAS), UA professor and AIDS researcher Nafees Ahmad, PhD, and his colleagues at the UA Department of Microbiology and Immunology looked at the mechanisms of differential HIV-1 infection in infants and adults. HIV-1 is a virus that causes AIDS. HIV-1 infected newborn babies and infants have a higher amount of circulating HIV-1 in their bodies and develop symptomatic AIDS faster than infected adults, including their own infected mothers. But the mechanisms of differential HIV-1 infection in infants and adults have not been known, Dr. Ahmad said.

By isolating immune cells, including T-lymphocytes and monocytes/macrophages from neonatal (cord blood) and adult blood, Dr. Ahmad's team of researchers found that HIV-1 multiplies more efficiently in neonatal cells than in adult cells and that the higher rate of HIV-1 multiplication in the neonatal immune cells is regulated at the level of HIV-1 gene expression.

HIV-1 gene expression occurs when the HIV-1 promoter is activated in the body to produce HIV-1 proteins, which are essential to making HIV, the AIDS virus. The study findings suggest that the neonatal cells make more HIV-1 proteins, compared with adult cells, contributing to a higher level of HIV-1 in the body and faster disease progression in newborns and infants than in adults.

The results of this study bring us closer to developing new and effective preventive and treatment methods for AIDS, says Dr. Ahmad. The data suggest that neonatal cells have different levels of cellular factors - factors that enhance the growth of the virus in the cell - compared with adult cells. The more virus the body makes, the faster AIDS develops. Because infants make more of the virus than adults, due to different levels of cellular factors, they develop AIDS, as well as several other infections, immunologic abnormalities and neurologic disorders, faster than adults. The cellular factors in newborns and infants that support efficient HIV-1 growth can be targeted with new drugs to inhibit the virus, says Dr. Ahmad.

Authors of the study, "Differential HIV-1 Replication in Neonatal and Adult Mononuclear cells is Influenced at the Level of HIV-1 Gene Expression," include Vasudha Sundaravaradan, PhD; Shailendra K. Saxena, PhD; Rajesh Ramakrishnan, PhD; Venkat R. K. Yedavalli, PhD; David T. Harris. PhD; and Nafees Ahmad, PhD.

The study will publish online in the Early Edition of PNAS on Wednesday, July 19, or Thursday, July 20, and will be available at www.pnas.org/cgi/doi/10.1073/pnas.0602185103. It also will be published in the Aug. 1 print edition of PNAS. Subscribers to EurekAlert! can access the study at www.eurekalert.org/pio/tipsheetdoc.php/237/zpq2990.pdf