Differences in CD4 molecules in human and chimpanzee

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malliga's picture
Differences in CD4 molecules in human and chimpanzee

     What is the difference between the CD 4 molecule of Human and Chimpanzee ?
   How CD4 helps in preventing  the  chimpanzee from HIV infection?
    Whether there is any difference in NK cells between human and chimpanzee ?

Arvind Singh Pundir
Arvind Singh Pundir's picture
A CD4 domain important for

A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site.
Camerini et. al., Volume 60, Issue 5, 9 March 1990, Pages 747-754 
Department of Genetics, Harvard Medical School, Boston, Massachusetts.

HIV infection of chimpanzees results in a chronic viremia unaccompanied by the ultimately fatal immunodeficiency that marks HIV infection in man. We show here that expression of HIV envelope proteins allows syncytium formation between cells expressing human but not chimpanzee or macaque CD4. We find that the CD4 sequences regulating cell fusion lie outside the recognized virus binding site; in the simplest exchange, chimpanzee CD4 bearing human residue 87 supports syncytium formation, while human CD4 bearing chimpanzee residue 87 does not. Neither the equilibrium nor the forward rate constants for HIV-CD4 association are affected by substitution at position 87. Infection of human cells expressing chimpanzee CD4 is insensitive to lysosomotropic agents, suggesting that viral penetration under these circumstances does not require endocytosis. The benign course of HIV infection in chimpanzees may reflect the failure of the host to support direct cell to cell transmission of the virus.
One difference between human and nonhuman primate CD4 is the inability of the latter to support syncytium formation. The study concluded that this was due to one amino acid difference (at position 87) between human and chimpanzee CD4. The study also reported that Rhesus CD4 shares 92% identity with human CD4. Below is a comparison of the amino acid sequences. 
HIV-infected humans, but not chimpanzees, have circulating cytotoxic T lymphocytes that lyse uninfected CD4+ cells
JM Zarling, JA Ledbetter, J Sias, P Fultz, J Eichberg, G Gjerset and PA Moran
Oncogen, Seattle, WA 98121.
The Journal of Immunology, Vol 144, Issue 8 2992-2998
It has been suggested that autoimmune phenomena contribute to the depletion of CD4+ T cells and the development of AIDS in HIV-1 infected humans based, in part, on observations that some HIV-1-infected humans have autoantibodies reactive with Ag expressed on uninfected CD4+ cells. In this study, 11 of 14 asymptomatic HIV-1-infected homosexuals and hemophiliacs, but none of 17 uninfected homosexuals or heterosexuals, were found to have cytotoxic lymphocytes in blood that can lyse uninfected CD4+ T cells from humans and chimpanzees but not human B lymphoblastoid cells or mouse T cells. The cytotoxic PBL were concluded to be CTL rather than NK cells, with the phenotype being CD3+, TCR-1 alpha beta+, CD8+, CD4-, CD16- based on findings that PBL- mediated lysis of uninfected CD4+ cells was 1) blocked by a mAb to CD3, which inhibits CTL but not NK activity; 2) diminished by treatment of PBL with a mAb to CD8 and C, but not by treatment with mAb to CD4 or CD16 and C; and 3) blocked by mAb WT31 directed against the TCR-1 alpha beta. In contrast, PBL from HIV-1-infected chimpanzees, which to date have not developed AIDS, lacked detectable CTL lytic for uninfected CD4+ cells