AEGiS-AIDS Weekly: Conference Coverage (SPIRAT/NCDDG-HIV): New HIV Trick: Beginning Replication Outside of Cells


(AW) Conference Coverage (SPIRAT/NCDDG-HIV): New HIV Trick: Beginning Replication Outside of Cells

AIDSWEEKLY Plus, Monday, 14 July 1997
Daniel J. DeNoon, Senior Editor


HIV can begin its replication process before entering cells, permitting it to infect quiescent cells previously thought to be virus resistant.

"HIV virions can be able, in the correct extracellular milieu, to reverse transcribe its RNA to DNA," said Roger J. Pomerantz of the Center for Human Virology at Thomas Jefferson University, Philadelphia, Pennsylvania.

Pomerantz announced the findings in a presentation to "New Opportunities for HIV Therapy - From Discovery to Clinical Proof-of-Concept," the 2nd Joint Conference of the National Institute of Allergy and Infectious Diseases (NIAID) Strategic Program for Innovative Research on AIDS Treatment (SPIRAT) and the National Cooperative Drug Discovery Groups for the Treatment of HIV Infection (NCDDG-HIV), held June 22-26, 1997, in Vienna, Virginia.

Intravirion reverse transcription represents "a new stage in the viral life cycle," Pomerantz said.

The phenomenon can occur only when the virions find themselves in an environment rich in deoxynucleoside 5'-triphosphates (dNTPs). Unfortunately, seminal fluid provides just such an environment.

Pomerantz noted that there are four ways HIV is carried within the seminal fluid:

* Cell-free virions can be found in the seminal fluid.

* The fluid harbors infected mononuclear cells.

* HIV is carried by infected spermatozoa and spermatozoal precursor cells.

* Virions can bind to the outside of sperm cells.

"This is of particular interest when you think of the testes/blood barrier, which is similar to the brain/blood barrier," Pomerantz said.

Cervical secretions, too, can harbor the virus, as can cervical macrophages, dendritic cells, and even epithelial cells of the cervical-vaginal mucosa.

"There are epithelial cells in the cervico-vaginal secretions that have HIV DNA in their nuclei," Pomerantz said.

The finding follows earlier reports that HIV is present in epithelial cells from gingival biopsies.

"The vast majority of patients had positive staining of gingival and salivary epithelia," Pomerantz noted. "Infection begins at the basal level."

These findings indicate that genital fluids and the genital mucosa represent an important viral reservoir. "HIV-1 may be found in a variety of different cell types within genital secretions, in different states of replication," Pomerantz wrote in his presentation abstract. "Further studies will be necessary to determine the importance of these unique cell-type reservoirs in patients treated with potent combination antiviral therapy, which appears to have extremely significant effects on HIV-1 replication in the peripheral blood and lymphoid tissue."

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