Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
Cloning and expression of primate CD4 molecules: diversity of the cellular receptor for SIV/HIV.
Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:48 (abstract no. 32). Unique Identifier : AIDSLINE PRIM8/900032 Fomsgaard A; Hirsch VM; McClure HM; Novembre FJ; Johnson PR; Department of Microbiology, Georgetown University and Laboratory; of Infectious Diseases, NIAID/NIH, Rockville, Md.
Abstract:
The pathogenic properties of non-human primate lentiviruses (SIV) are varied, and may depend in part on host-specific factors. Biologic disparity among SIVs also extends to infection of cells in culture, where significant differences in cellular tropisms and cytopathic effects are observed. One potential determinant of SIV tropism and pathogenecity is the process of entry into target cells via the cellular receptor, CD4. To study the SIV/HIV-CD4 interaction, we have undertaken cloning and expression of CD4 molecules from six non-human primate species: African green monkeys (3 distinct subspecies), sooty mangabeys, patas monkeys, chimpanzees, rhesus macaques, and pig-tailed macaques. Molecular clones representing CD4 mRNAs were generated from total cellular RNA (from PBMCs) by PCR amplification. Primer sequences were selected from regions conserved among human and rodent CD4 genes. Alignments of deduced amino acid sequences revealed several interesting findings. First, all of the primate CD4 molecules were about 90% identical to the human CD4 sequence except the chimpanzee (about 98%). Second, two macaque subspecies or two African green monkey subspecies were as closely related as the human versus chimpanzee sequences. Third, relatedness of CD4 sequences could not be predicted on the basis of geographic origin (Asian vs. African). Finally, two distinct populations of CD4 molecules were present in 3 of 4 sooty mangabeys examined. The distinguishing feature was a single amino acid deletion (relative to a primate consensus sequence) in the CDR-1 region of V1J1, a domain implicated in CD4/HIV-1 interactions. Overall, the V1J1 domain was the most variable region among all the sequences examined. To further examine the importance of CD4 sequence diversity, strategies were devised to construct and express chimeric CD4 mRNAs between human and non-human primate sequences. To date, 7 chimeras have been generated and expressed in mammalian cell lines of human (293 cells), macaque (LLC-MK2), or African green monkey (CV-1) origin. These genetically-engineered cell lines will be useful for defining domains important for SIV/CD4 interactions and providing species-specific cell lines for assays of virus infectivity.
Keywords: Animal Antigens, CD4/*GENETICS Cell Line Chimera Chimpansee troglodytes Cloning, Molecular Human HIV-1/IMMUNOLOGY Macaca Mutation Polymerase Chain Reaction Receptors, HIV/*GENETICS Receptors, Virus/*GENETICS Rodentia RNA, Messenger/BIOSYNTHESIS Sequence Homology, Nucleic Acid *Variation (Genetics) ABSTRACT 910730
M9170962
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
