Human genes other than CD4 facilitate HIV-1 infection of murine cells.
The human CD4 glycoprotein is a specific receptor for the HIV family of retroviruses. When expressed on human cell lines, this molecule binds virus through direct interactions with the gp 120 viral envelope glycoprotein thus allowing virus infection to occur. Subsequent to binding, conformational changes in the viral envelope glycoproteins are thought to facilitate virus entry into the target cell through direct fusion of the virus with the cell membrane. In contrast to the infection observed in human cell lines, infection of murine cell lines even in the presence of the CD4 receptor does not readily occur. We have examined this species tropism of HIV infection. We report that the inability to infect murine cells is not a function of the receptor for HIV or a suppressive function of the murine cellular background. Human CD4 expression, configuration and down-modulation on the murine background are similar if not identical to expression on the human cell background. Utilizing a panel of interspecific cell hybridomas, we have been able to bypass the barrier to infectivity of human CD4-positive murine cells. We demonstrate that there are at least two different restrictions to infectivity on the mouse background which can be complemented by the human genome. One restriction appears to be an extremely early postbinding function likely to be molecules necessary for viral entry into cells, the second restriction is necessary for high levels of virus production. Our mapping studies suggest that fewer than five human chromosomes are necessary for reconstituting infectivity in the murine background. These results have implications for models of HIV-induced pathogenesis and infectivity.
Wistar Institute, Department of Medicine, University of Pennsylvania, Philadelphia.
D B
DB
Weiner
K
K
Huebner
W V
WV
Williams
M I
MI
Greene
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000382:microbiology / Q000473:pathology; D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002874:Chromosome Mapping; D003110:Colonic Neoplasms / Q000382:microbiology / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000382:microbiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005796:Genes / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology / Q000382:microbiology*; D051379:Mice; D011533:Proviruses / Q000502:physiology; D014162:Transfection
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120