Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Selection of an SIVmac LTR sequence upon mucosal inoculation of rhesus macaques.
Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 13. Unique Identifier : AIDSLINE PRIM11/94191605 Meyer KK; Trivedi P; Streblow DN; Emau P; Pauza CD; University of Wisconsin, Madison 53706.
Abstract:
The primate retroviruses SIV and HIV, develop into complex virus populations in infected hosts. A less complex virus subset is established upon sexual transmission of HIV in man. The loss of complexity during transmission may be due to a titration effect (inefficient transmission or low doses of virus in the inoculum) or to a selection mechanism operating at the mucosa. Direct sequence comparison of SIV populations in rhesus monkeys following intravenous and intrarectal inoculation showed that the reduced complexity resulted from a selection mechanism. One year old juvenile rhesus monkeys were inoculated intravenously (10 ID) or intrarectally (0.1 or 100 ID) with a biological isolate of SIVmac. Samples at 8 weeks after inoculation were positive for viral DNA in peripheral blood mononuclear cells (PBMC) from all animals. PBMC DNA samples were used as templates for polymerase chain reaction amplification of the viral long terminal repeat (LTR); these fragments were cloned and sequenced. The nature of the inoculum was also evaluated through short-term, in vitro infection of CEMx174 cells, DNA purification, LTR amplification, cloning and sequencing. Two predominant LTR sequences were observed; LTR containing 3 SP1 sites (similar to the previously reported sequence of molecular clone SIVmac239) and LTR containing 2 Sp1 sites (similar to the sequence of molecular clone SIVmac251). Single nucleotide variants were also observed although they were not considered for the purposes of this comparison. The inoculum exhibited a ratio of 9:1 for LTR with 3 SP1 sites predominating; an identical ratio was observed for intravenously infected animals. Intrarectally (i.r.) infected animals showed a skewed ratio. High dose i.r. animals manifested a 15:85 ratio (predominantly LTR with 2 SP1 sites) and the low dose i.r. animals contained only LTR with 2 SP1 sites. Precautions to guard against sampling errors or contamination in DNA amplification were taken. These results support the hypothesis that the mucosa represents a selective barrier to virus. The barrier acts to reduce virus population complexity during intramucosal transmission. These data suggest that an effective mucosal vaccine may need to target only a limited portion of the complex virus population.
Keywords: Animal Blood Transfusion DNA, Viral/BLOOD Gene Products, env/*GENETICS Intestinal Mucosa/*MICROBIOLOGY Leukocytes, Mononuclear/MICROBIOLOGY Macaca mulatta Polymerase Chain Reaction/METHODS Rectum *Repetitive Sequences, Nucleic Acid Retroviridae Proteins, Oncogenic/*GENETICS Simian Acquired Immunodeficiency Syndrome/MICROBIOLOGY/ *TRANSMISSION SIV/GENETICS/*ISOLATION & PURIF Viral Fusion Proteins/*GENETICS ABSTRACT 940730
M9470913
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
