3rd International Workshop on HIV Drug Resistance 2-5 August 1994, Kauai, Hawaii, USA

IDENTIFICATION OF A CLINICAL ISOLATE OF HIV-1 FROM NORTHERN THAILAND WITH A NATURALLY OCCURRING ISOLEUCINE AT POSITION 82 OF THE PROTEASE

Int Wkshop HIV Drug Res 1994 Aug 2-5;3:19 (abstract no. 18)

Robert W. King, Dean L. Winslow, Sena Garber, Helen Scarnati, Sylvia Stack, and Michael J. Otto
The DuPont Merck Pharmaceutical Co., Glenolden PA USA 19036

The HIV-1 protease contains five highly conserved regions. These include the sites for dimer formation, the catalytic site, the flap, and the substrate binding pocket. Variants in the S1/S l´ subsite of the pocket have been isolated but only after passage in the presence of protease inhibitors. Specifically, variations have been found at amino acids 82 and 84. We previously reported the selection of variants which contained either V82A or V82F changes which were less susceptible to protease inhibitors in the C2 symmetrical dial and cyclic urea classes. We now report the identification of a clinical isolate of HIV-1, designated HIV-1 (Th 16), which contained a naturally occurring isoleucine at position 82. This virus was isolated from an asymptomatic, heterosexual male from Chaing Mai, Thailand who had not been treated with any anti-retroviral agent. While isoleucine is commonly found at the equivalent position in the protease of HIV-2, we are unaware of any other example of an isoleucine being found at this location in a clinical isolate of HIV-1. When HIV-1 (Th 16) was tested for its susceptibility to examples of several classes of protease inhibitors (XM323, Ro31-8959, P9941, and A-80987), it exhibited the same sensitivities as the V82 wild type. Thus, unlike V82A or V82F, the V82I difference does not alter the susceptibility of the virus to these inhibitors of HIV-1 protease.

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1994-08-02
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