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Science 8 August 1986:
Vol. 233. no. 4764, pp. 655 - 659
DOI: 10.1126/science.3014663
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Articles

Science, Vol 233, Issue 4764, 655-659
Copyright © 1986 by American Association for the Advancement of Science

articles

Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects

AG Fisher, L Ratner, H Mitsuya, LM Marselle, ME Harper, S Broder, RC Gallo, and F Wong-Staal

A variant of human T-lymphotropic virus type III (HTLV-III) is described that replicates but does not kill normal human T cells in vitro. This variant, designated X10-1, was derived from the genome of a cytopathic HTLV-III clone (pHXB2D) by excision of a 200-base pair segment in the 3' region of the virus, spanning the env and 3'-orf genes. Comparable variants with 55 to 109 base pairs deleted exclusively in 3'-orf produced, in contrast, virus that was extremely cytopathic. On the basis of these findings it is concluded that the 3'-orf gene is not required for cytopathogenicity or replication of HTLV-III. In addition, the results suggest that virus replication and cytotoxicity are not intrinsically coupled. Furthermore, since clone X10-1 retains the ability to trans-activate genes linked to the viral long terminal repeats, trans-activation per se is not responsible for T-cell killing by HTLV-III. These results also raise the possibility that the carboxyl terminus of the envelope gene of HTLV-III has a direct role in T-cell killing by this virus.


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