Murine T cells potently restrict human immunodeficiency virus infection.
Development of a mouse model for human immunodeficiency virus type 1 (HIV-1) infection has advanced through the progressive identification of host cell factors required for HIV-1 replication. Murine cells lack HIV-1 receptor molecules, do not support efficient viral gene expression, and lack factors necessary for the assembly and release of virions. Many of these blocks have been described using mouse fibroblast cell lines. Here we identify a postentry block to HIV-1 infection in mouse T-cell lines that has not been detected in mouse fibroblasts. While murine fibroblastic lines are comparable to human T-cell lines in permissivity to HIV-1 transduction, infection of murine T cells is 100-fold less efficient. Virus entry occurs efficiently in murine T cells. However, reduced efficiency of the completion of reverse transcription and nuclear transfer of the viral preintegration complex are observed. Although this block has similarities to the restriction of murine retroviruses by Fv1, there is no correlation of HIV-1 susceptibility with cellular Fv1 genotypes. In addition, the block to HIV-1 infection in murine T-cell lines cannot be saturated by a high virus dose. Further studies of this newly identified block may lend insight into the early events of retroviral replication and reveal new targets for antiretroviral interventions.
Baumann
Jörg G
JG
HIV Drug Resistance Program, Bldg. 535, Rm. 123, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.
Unutmaz
Derya
D
Miller
Michael D
MD
Breun
Sabine K J
SK
Grill
Stacy M
SM
Mirro
Jane
J
Littman
Dan R
DR
Rein
Alan
A
KewalRamani
Vineet N
VN
D000818:Animals; D015870:Gene Expression; D005838:Genotype; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000502:physiology; D041681:NIH 3T3 Cells; D011506:Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D014158:Transcription, Genetic
C103189:Fv1 protein, mouse; D011506:Proteins