Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Intramucosal transmission of primate retroviruses.
Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 2. Unique Identifier : AIDSLINE PRIM11/94191612 Pauza CD; Trivedi P; Meyer KK; Streblow DN; Malkovsky M; Salvato MS; Schultz KT; Emau P; Wisconsin Regional Primate Research Center, University of; Wisconsin, Madison 53706.
Abstract:
The development of vaccines to block sexual transmission of HIV-1 in man, requires a thorough understanding of factors affecting intramucosal transmission. In particular, it is necessary to determine the inoculum size and complexity, the relationship between virus dose and disease progression, the factors affecting infectiousness and susceptibility, and to describe completely the portal of entry. We have approached some of these problems in the rhesus monkey system using SIVmac as the prototypic virus. Detailed study of juvenile males inoculated intrarectally with SIVmac illustrated the profound relationship between virus dose, route of inoculation and disease progression. High virus doses administered intrarectally without trauma, induced rapid seroconversion, elevated viremia, and clinical disease progression although clinical signs evolved slowly in comparison to intravenous infection controls. Low doses administered intrarectally established no detectable viremia, there were few evident clinical signs, and seroconversion was only noted at 2 years after inoculation. The unusual features of intrarectal infection were due in part, to a selection for virus sequences at the mucosal barrier. Molecular cloning and sequencing studies for long terminal repeat and envelope gene regions, demonstrated that only a limited portion of the complex virus population was capable of crossing the mucosal barrier. These viruses were associated with slow disease progression even in animals inoculated by transfusion. Intramucosal transmission studies attest to a complex relationship between dose, route of administration and disease progression. These studies highlight the role of host immunity in forestalling disease progression and the consequences of selecting less pathogenic variants during transmission. Moreover, our data promote the development of mucosal vaccines by indicating that few virus sequences are capable of efficient intramucosal transmission.
Keywords: Acquired Immunodeficiency Syndrome/PREVENTION & CONTROL/ TRANSMISSION Animal Cloning, Molecular Human HIV-1 Intestinal Mucosa/*MICROBIOLOGY Macaca mulatta Rectum Sexually Transmitted Diseases/PREVENTION & CONTROL/TRANSMISSION Simian Acquired Immunodeficiency Syndrome/IMMUNOLOGY/ *TRANSMISSION *SIV/ISOLATION & PURIF ABSTRACT 940730
M9470906
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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.
