4th International AIDS Conference


Stockholm, Sweden. — June 12-16, 1988

[TITLE:] ANALYSIS OF THE FUNCTIONS OF THE HIV-1 R AND 3'ORF GENE PRODUCTS

Int Conf AIDS. 1988 Jun 12-16;4:1.116 (abstract no. 1014)

Lee Ratner and Thomas Niederman
Department of Medicine, Washington University, St. Louis, MO, USA

HIV-1 is an unusual retrovirus with 8 genes, only 3 of which are known to encode virion proteins. The functions of 2 of its gene products, designated R arid 3'orf have remained obscure. These proteins are predicted to be conserved among different HIV-1 isolates as well as with those of simian immunodeficiency virus and HIV-2.

To define the role of the potential 78 amino acid R protein, a frameshift HIV-1 mutant was constructed which would encode a truncated protein of only 43 amino acids. The R, HIV-1 proviral clone yielded virus which shaved similar infectivity, replication rate, and cytopathicity to that of the R+ HIV-1 parental virus in several different lymphoid and monocytoid cell lines. 1-No differences were seen in viral T,NAs, RNAs, and proteins in cells infected with the R. HIV-1 mutant compared to the R+ HIV-1 virus.

3'Orf frameshift and deletion mutants of HIV-1 were constructed, and viruses derived from these clones were found in every case to replicate at significantly higher levels than the 3'orf+ HIV-1 virus. In T4- cells, this regulatory effect was localized to a step in the latter half of the virus life cycle, involving transcription, translation, or virus assembly or release. However, no effects were seen on transcription or trans-activation using HIV-1 LTR CAT assays. In experiments in which 3'orf- and 3'orf+ clones were transfected into the same culture, the phenotype of the 3'orf- virus was dominant.

These data suggest that 1) R encodes a protein which is not required for HIV-1 replication and cytopathicity' and 2) 3'orf acts as a negative regulator affecting a late step in the virus life cycle.

880612
1014

Copyright © 1988 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.