Depletion of the surface CD4 molecule by the envelope protein of human immunodeficiency virus expressed in a human CD4+ monocytoid cell line.
A CD4+ human monocytoid cell line, U937, was transfected with a constructed plasmid which has the envelope gene of human immunodeficiency virus under the transcriptional control of the human metallothionein IIA promoter and was cloned thereafter. These cloned cell lines (EH and EL cells) expressed the viral gp160 in the cytoplasm. The expression of surface CD4 antigen examined by Leu3a and OKT4 monoclonal antibodies, however, disappeared completely in EH cells, which produce a larger amount of gp160, while diminishing only partly in EL cells, which produce a smaller amount of gp160. These results indicate that the level of expression of surface CD4 antigen correlates inversely with the amount of intracellular gp160. Moreover, immunoprecipitation studies using lysate from EH cells showed that OKT4 monoclonal antibody precipitated a significant number of CD4 molecules even after surface CD4 disappeared. However, Leu3a monoclonal antibody, which recognizes the binding site for envelope protein, could not precipitate any CD4 molecules in the same cell lysate. Taken together, these results suggested that CD4 molecules are still synthesized normally after the augmented production of gp160 in the cells but form a complex with the envelope protein in the cytoplasm and become unable to be transported to the cell surface, resulting in the observed depletion of surface CD4 antigen. This mechanism may explain the decrease or absence of surface CD4 antigens in human lymphocytes infected with human immunodeficiency virus.
Kawamura
I
I
Department of Immunology, Kyushu University, Fukuoka, Japan.
Koga
Y
Y
Oh-Hori
N
N
Onodera
K
K
Kimura
G
G
Nomoto
K
K
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D002460:Cell Line; D003593:Cytoplasm / Q000032:analysis; D005814:Genes, Viral; D019302:HIV Envelope Protein gp160; D006801:Humans; D011233:Precipitin Tests; D012191:Retroviridae Proteins / Q000032:analysis* / Q000235:genetics; D014162:Transfection; D014759:Viral Envelope Proteins / Q000032:analysis* / Q000235:genetics
D000945:Antigens, Differentiation, T-Lymphocyte; D019302:HIV Envelope Protein gp160; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins