Sepsis Research Today is a free monthly online journal that collates and summarizes the latest research about Sepsis, including details on septicemia, diagnosis, symptoms, treatment. | ||||||||
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Comparison of plasma viremia and antibody responses in macaques inoculated with envelope variants of single-cycle simian immunodeficiency virus differing in infectivity and cellular tropism.DeGottardi MQ, Lew SK, Piatak M, Jia B, Feng Y, Lee SJ, Brenchley JM, Douek DC, Kodama T, Lifson JD, Evans DT Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, One Pine Hill Drive, Southborough, MA 01772-9102, USA. Molecular differences in the envelope glycoproteins of human immunodeficiency virus type 1 and simian immunodeficiency virus (SIV) determine virus infectivity and cellular tropism. To examine how these properties contribute to productive infection in vivo, rhesus macaques were inoculated with strains of single-cycle SIV (scSIV) engineered to express three different envelope glycoproteins with full-length (TM(open)) or truncated (TM(stop)) cytoplasmic tails. The 239 envelope uses CCR5 for infection of memory CD4(+) T cells, the 316 envelope also uses CCR5 but has enhanced infectivity for primary macrophages, and the 155T3 envelope uses CXCR4 for infection of both naive and memory CD4(+) T cells. Separate groups of six rhesus macaques were inoculated intravenously with mixtures of TM(open) and TM(stop) scSIV(mac)239, scSIV(mac)316, and scSIV(mac)155T3. A multiplex real-time PCR assay specific for unique sequence tags engineered into each virus was then used to measure viral loads for each strain independently. Viral loads in plasma peaked on day 4 for each strain and were resolved below the threshold of detection within 4 to 10 weeks. Truncation of the envelope cytoplasmic tail significantly increased the peak of viremia for all three envelope variants and the titer of SIV-specific antibody responses. Although peak viremias were similar for both R5- and X4-tropic viruses, clearance of scSIV(mac)155T3 TM(stop) was significantly delayed relative to the other strains, possibly reflecting the infection of a CXCR4(+) cell population that is less susceptible to the cytopathic effects of virus infection. These studies reveal differences in the peaks and durations of a single round of productive infection that reflect envelope-specific differences in infectivity, chemokine receptor specificity, and cellular tropism. Published 11 December 2007 in J Virol, 82(1): 321-34.
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