Species tropism of chimeric SHIV clones containing HIV-1 subtype-A and subtype-E envelope genes.
To analyze HIV-1 genes in a nonhuman primate model for lentivirus infection and AIDS, recombinant SIV/HIV-1 (SHIV) clones were constructed from two HIV-1 subtype-A isolates (HIV-1(SF170) and HIV-1(Q23-17) from individuals in Africa) and two HIV-1 subtype-E isolates (HIV-1(9466) and HIV-1(CAR402) from AIDS patients in Thailand and Africa), respectively. These four SHIV clones, designated SHIV-A-170, SHIV-A-Q23, SHIV-9466.33, and SHIV-E-CAR, contain envelope (env) genes from the subtype-A or -E viruses. Interestingly, SHIV-A-170, SHIV-A-Q23, and SHIV-9466.33 were restricted for replication in cultures of macaque lymphoid cells, whereas SHIV-E-CAR replicated efficiently in these cells. Additional studies to define the block to replication in macaque cells were focused on the subtype-E clone SHIV-9466.33. A SHIV intragenic env clone, containing sequence-encompassing V1/V2 regions of HIV-1(CAR402) and V3/V4/V5 regions of SHIV-9466.33, infected and replicated in macaque lymphoid cells. These results indicated that the sequence-encompassing V1/V2 region of HIV-1(9466) was responsible for the block of the SHIV-9466.33 replication in macaque cells. Analysis of viral DNA in acutely infected macaque cells revealed that SHIV-9466.33 was blocked at a step at/or before viral DNA synthesis, presumably during the process of virion entry into cells. In a fluorescence-based cell-cell fusion assay, fusion pore formation readily took place in cocultures of cells expressing the SHIV-9466.33 env glycoprotein with macaque T-lymphoid cells. Taken together, these results demonstrated that the block of SHIV-9466.33 replication in macaque cells is at an early step after fusion pore formation but before reverse transcription.
Himathongkham
Sunee
S
Center for Comparative Medicine, University of California, Davis, CA 95616, USA.
Douglas
Gordon C
GC
Fang
Adrienne
A
Yu
Emily
E
Barnett
Susan W
SW
Luciw
Paul A
PA
D000818:Animals; D002478:Cells, Cultured; D015686:Gene Products, env / Q000235:genetics; D005822:Genetic Vectors; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007668:Kidney; D010446:Peptide Fragments / Q000502:physiology; D016865:Reassortant Viruses / Q000235:genetics / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D013601:T-Lymphocytes; D014779:Virus Replication
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; C059761:HIV envelope protein gp120 (135-148); D010446:Peptide Fragments