Important note: Information in this article was accurate in April 2001. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, April 9, 2001
Michael Greer, Staff Medical Writer
NewsRx - HIV variants that do not need the presence of CD4 for cell entry are less resistant to immune activity than the normal virus, which may account the rarity of such strains, researchers report.
"In the laboratory, HIV-1 variants that are capable of bypassing CD4 and utilizing only the CCR5 chemokine receptor for virus entry have been generated," explained J. Sodroski and colleagues at the Dana Farber Cancer Institute.
Sodroski et al. showed why such viruses, which would presumably have a significant competitive advantage over their CD4-requiring brethren, are not more common in the wild: they are significantly more susceptible to neutralization.
The same alterations in the HIV envelope glycoprotein gp120 amino acids that confer CD4 independence also make this variant much more vulnerable to neutralization by antibodies and, ironically, to soluble CD4, they said.
Envelope proteins in the CD4-independent variant were more susceptible to antibodies targeting CD4-induced gp120 epitopes, study data showed, although other neutralizing agents received no such advantage.
Despite this increased vulnerability, CD4-independent envelope glycoproteins were as stable as their wild-type counterparts ("Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants," Journal of Virology, March 2001;75(5):2041-2050).
"The utilization of two receptors apparently allows HIV-1 to maintain a more neutralization-resistant state prior to engaging CD4 on the target cell, explaining the rarity of CD4 independence in wild-type HIV-1," Sodroski and colleagues concluded.
The corresponding author for this report is J. Sodroski, Dana Farber Cancer Institute, Dept. of Cancer Immunology and AIDS, 44 Binney Street, JFB 824, Boston, MA 02115 USA.
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
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