Infection of human and non-human cells by a highly fusogenic primary CD4-independent HIV-1 isolate with a truncated envelope cytoplasmic tail.
Truncation of the envelope cytoplasmic tail has enabled FIV, SIV, and some laboratory HIV-1 strains to acquire broader cellular tropism and enhanced fusogenicity. Here we have characterized a primary CD4-independent HIV-1 isolate (92UG046-T8) with a truncated cytoplasmic tail that was able to infect and induce syncytia in primary lymphocytes from human, chimpanzee, and monkey, as well as CD4-negative cell lines from human and monkey. Increased syncytia were also noticeable with 293 cells expressing the cloned envelope from the 92UG046-T8 isolate suggesting envelope-mediated cellular fusion. Except pooled serum from HIV-1-infected individuals, monoclonal anti-envelope antibodies or antibodies/antagonists against CD4, CXCR4, and CCR5 were not able to prevent infection by the 92UG046-T8 isolate. This is the first report showing a primary HIV-1 variant with truncated cytoplasmic tail which is highly fusogenic and can infect a broad range of cells from human and non-human origins. In vivo evolution of similar HIV-1 mutants may have important implications in AIDS pathogenesis.
Saha
Kunal
K
Department of Pediatrics and Molecular Virology, Immunology and Medical Genetics, Children's Research Institute and Ohio State University Medical Center, Columbus, 43205, USA. sahak@pediatrics.ohio-state.edu
Yan
Hui
H
Nelson
Julie A E
JA
Zerhouni-Layachi
Bouchra
B
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D017353:Gene Deletion; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D014759:Viral Envelope Proteins / Q000235:genetics*
D015704:CD4 Antigens; D014759:Viral Envelope Proteins