Altered replication of human immunodeficiency virus type 1 (HIV-1) in T cell lines retrovirally transduced to express Herpesvirus saimiri proteins StpC and/or Tip.
Human peripheral blood T lymphocytes are transformed in vitro to continuous proliferation by Herpesvirus saimiri subgroup C strains. It has been previously shown that H. saimiri-transformed human T cell lines are a permissive system for HIV-1 and 2 replication and are highly susceptible to infection by HIV-1 and 2. Two open reading frames of H. saimiri, StpC and Tip, are required for T cell transformation and are unique to this herpesvirus. The successful transduction of human T cells with retroviral vectors expressing H. saimiri proteins StpC and Tip has allowed us to extend the previously mentioned observations and investigate the role of StpC and Tip in replication of HIV-1 T-tropic strains (IIIB, MN, and RF) in human T cell lines. StpC expression in Molt4 dramatically enhanced HIV-1 replication as measured by Tat protein expression, syncytia formation, and accumulation of reverse transcriptase activity. In contrast, Tip expression in Molt4 cells inhibited HIV-1 replication and cytopathic effects relative to Molt4 cells transduced with the empty vector alone. The StpC-induced phenotype dominated in Molt4 cells transduced to express both StpC and Tip, suggesting that StpC is responsible for facilitating HIV-1 replication in H. saimiri-transformed T cells. Colony-forming ability of Tip-expressing Molt4 cells following HIV-1 infection was greatly enhanced over Molt4 cells expressing either StpC or no H. saimiri proteins at all. HIV-1 proviral DNA could be detected by PCR in surviving Molt4 cells expressing StpC or Tip, indicating that a persistent infection was established. A better understanding of the effects of Tip and StpC proteins on the biology of human hemopoietic stem cells may lead to novel therapeutic interventions for the treatment of AIDS.
Henderson
E E
EE
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. eehender@astro.temple.edu
Tsygankov
A Y
AY
Merlo
J J
JJ
Romano
G
G
Guan
M
M
D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015752:Genes, env; D015751:Genes, pol; D015726:Giant Cells; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D006801:Humans; D016366:Open Reading Frames; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000821:virology*; D014161:Transduction, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
D004279:DNA, Viral; D010750:Phosphoproteins; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2