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Scientists discover how HIV enters cells

BMJ 1996; 312 doi: https://doi.org/10.1136/bmj.312.7047.1628a (Published 29 June 1996) Cite this as: BMJ 1996;312:1628

A new, recently discovered cofactor that allows HIV-1 to enter and infect human cells could prove a useful future therapeutic target, according to US scientists writing in the 28 June issue of Science (272;1955-8).

HIV-1 infects cells by binding to the cell surface molecule called CD4. Although this mechanism has been recognised for the past decade, researchers had noted that the presence of CD4 alone was not sufficient to guarantee infection. It became clear that a cofactor was needed.

One of the authors of this recent paper is Edward Berger, chief of the molecular structure section at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland, United States.

Berger said: “We knew that the basic mechanism was rather like two soap bubbles: a large one representing the cells, and a small one, the virus. They stuck to each other, but their contents did not mix. It was this mechanism of viral mixing which we all knew to be crucial, but no one understood how it was achieved.”

Figure1

Now we know how HIV gets into cells

Last month scientists from Dr Berger's team identified the cofactor as fusin, a molecule that allows HIV to fuse with its target before entry (Science;272:872-7). However, only certain strains of HIV-1—those identified in the late stages of HIV infection—seemed to need this cofactor. Other strains, most commonly passed between individuals in the early stages of the infection, seem to have a different mechanism for entering cells.

Along with other teams of colleagues, who published an article in the 20 June issue of Nature (381;667-673), part of the same research group has identified a second fusin-type molecule called CC CKR5. Unlike fusin, which is found on T cells, CC CKR5 is found on macrophages.

CC CKR5 is a receptor for chemokines known to inhibit HIV infection. Chemokines have been shown to stop in vitro replication of HIV. They may achieve this by blocking HIV's access to their receptors, which act as viral docking sites.

“The number and distribution of these cofactors may help to explain why some individuals stay asymptomatic for a long time, while others become rapidly infected with HIV and progress to full blown AIDS faster,” said Dr Berger. The race is now on to create transgenic animal models that have not only human CD4 receptors but also the two newly identified cofactors, fusin and CC CKR5.

“Many of the therapeutic implications of this discovery remain speculative, but we have reached a better understanding of a vital process in HIV infection which has remained unclear until now,” said Dr Berger.—ALISON BOULTON, freelance journalist, London

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