Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4.
Binding of the human immunodeficiency virus (HIV) to infectable host cells, such as B and T lymphocytes, monocytes and colorectal cells, is mediated by a high-affinity interaction between the gp120 component of the viral envelope glycoprotein and the CD4 receptor. Upon binding, it is thought that the second component of the envelope, gp41, mediates fusion between the viral envelope and host cell membranes. However, the early steps of HIV infection have not yet been thoroughly elucidated. Viral entry was first reported to be mediated by pH-dependent receptor-mediated endocytosis; subsequent studies have shown entry to be pH-independent. Although direct fusion of virus to plasma membranes of infected cells has been observed by electron microscopy, it is still formally possible that the infectious path of the virus involves receptor-mediated endocytosis. To gain a better understanding of receptor function in viral entry, we have analysed the ability of several altered or truncated forms of CD4 to serve as effective viral receptors. Our results indicate that domains beyond the HIV-binding region of CD4 are not required for viral infection. Some of the altered forms of CD4 that serve as effective HIV receptors are severely impaired in their ability to be endocytosed. These experiments therefore support the notion that viral fusion to the plasma membrane is sufficient for infection.
Bedinger
P
P
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Moriarty
A
A
von Borstel
R C
RC
Donovan
N J
NJ
Steimer
K S
KS
Littman
D R
DR
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004705:Endocytosis; D006678:HIV / Q000378:metabolism*; D006801:Humans; D010703:Phorbol Esters / Q000494:pharmacology; D011991:Receptors, Virus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000382:microbiology / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D010703:Phorbol Esters; D011991:Receptors, Virus