Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
NOVEL ENDOGENOUS SEQUENCES RELATED TO HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
Diss Abstr Int [B]; 52(6):2911 1991. Unique Identifier : AIDSLINE ICDB/92679369 Horwitz MS; Univ. of Minnesota
Abstract:
Endogenous retroviral-related sequences exist within normal genomic DNA of all eukaryotes and have importance to the nature and biology of related exogenous retroviruses, as well as, play roles in cellular functions. Human immunodeficiency virus type-1, the purported causative agent of acquired immunodeficiency syndrome, was identified only within the last decade and, as yet, no related endogenous sequences have been reported. If found, endogenous HIV-1-related sequences may play an active role in the biology and/or evolution of HIV-1. Endogenous HIV-1-related sequences would represent either a related endogenous retrovirus or an exon of a cellular gene with a similar functional domain. This is the first report of the presence of nucleotide sequences related to HIV-1 in primate genomic DNA of normal uninfected individuals. Two strategies, low stringency hybridization (LSH) with HIV-1-derived probes and polymerase chain reactions with HIV-1-derived primers under reduced annealing conditions, were employed. Using LSH, complex banding patterns were detected in primate genomic DNA with HIV-1 probes. PCR analysis directed at functional domains of HIV-1 gag and env identified the amplification of primate sequences which hybridize to HIV-1. Two endogenous HIV-1-related sequences, EHS-1 and EHS-2, were isolated from normal human genomic DNA libraries using env probes. Characterization of EHS-1 and -2 showed limited sequence homology to HIV-1 across regions encoding functional domains of HIV-1; however, neither clone contains any obvious retroviral structure and most likely represents cellular sequences encoding similar functional domains. EHS-1 has sequence and structural similarity with the envelope cellular protease cleavage site of HIV-1, while EHS-2 has sequence and structural similarity to the RNA binding domain of Rev. Southern blot and PCR analysis showed both EHS-1 and -2 to be highly conserved loci within the primates and minor family members of the large EHS family detected by LSH; many members remain unisolated. Oligonucleotide probes derived from EHS-2 and HIV-1 rev detect the EHS family identified under LSH and differential expression of mRNAs suggesting that most EHS share a core of nucleic acid found in EHS-2 and rev, some have flanking regions with additional similarity to HIV-1, and some are expressed. Further analysis of these and other EHS will help determine whether such endogenous sequences have any influence on HIV-1 pathogenesis or have contributed to the evolution of HIV-1. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-34508).
Keywords: *Amino Acid Sequence DNA Probes DNA, Viral/GENETICS Gene Amplification Gene Products, env/GENETICS Gene Products, gag/GENETICS Gene Products, rev/GENETICS Genome, Viral HIV-1/*GENETICS/METABOLISM Nucleic Acid Hybridization Polymerase Chain Reaction RNA, Viral/METABOLISM THESIS 920630
M9261022
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