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.
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.
DeGottardi
M Quinn
MQ
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, One Pine Hill Drive, Southborough, MA 01772-9102, USA.
Lew
Sharon K
SK
Piatak
Michael
M
Jia
Bin
B
Feng
Yang
Y
Lee
Sandra J
SJ
Brenchley
Jason M
JM
Douek
Daniel C
DC
Kodama
Toshiaki
T
Lifson
Jeffrey D
JD
Evans
David T
DT
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D008253:Macaca mulatta; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics*; D019562:Viral Load; D014766:Viremia
D000914:Antibodies, Viral; D014759:Viral Envelope Proteins