Abstract:
Recently investigations of SIV and HIV infections have demonstrated that the viral burden in the peripheral blood vastly underestimates the extent of lymphoid involvement. Therefore, tissues may be a reservoir for viruses of different biologic and pathogenic properties than those observed in the blood. However, little is known about the extent of genetic heterogeneity of primate lentiviruses within or between tissues of an infected animal. Such variation, particularly in the envelope, could greatly impact cellular tropism or aid in evasion of the host immune response. In the present study, the envelope heterogeneity in various tissues and peripheral blood mononuclear cells (PBMC) from two SIV infected macaques with encephalitis was investigated using single stranded conformational polymorphism (SSCP) as a screening assay, followed by sequence analysis. The two animals followed different courses of disease, one never developed a strong Ab response to SIV and died within one year post infection (Pt56), while the other macaque followed a more prolonged course and died after three years (E543). The most variable region (V1) of the SIV envelope and the region encompassing the V3 loop analog were evaluated. Our analysis demonstrated considerable heterogeneity in both regions in all tissues examined. However, the degree of heterogeneity was highly variable in a tissue dependent manner. While there was limited heterogeneity in the brain, and PBMCs, marked heterogeneity was seen in the spleen and lymph nodes of the same animal. The V1 region was the most variable of the two domains evaluated whereas variation in the V3 analog was generally confined to three residues in both animals. Variations in two of these residues have previously been shown to alter tropism in tissue-derived clones isolated in this laboratory. Infectious clones from tissues that differ in the three residues in the V3 analog are currently being evaluated for changes in cellular tropism. This study demonstrates that virus populations in PBMC can greatly underestimate the potential burden of viral variants in an infected animal.
Keywords: Animal Encephalitis/ETIOLOGY/MICROBIOLOGY Gene Products, env/GENETICS *Genes, env Lymphocytes/MICROBIOLOGY Macaca Polymorphism (Genetics) Simian Acquired Immunodeficiency Syndrome/COMPLICATIONS/ *MICROBIOLOGY SIV/*GENETICS/ISOLATION & PURIF Variation (Genetics) ABSTRACT 940730
M9470893
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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.
