Analysis of Genetic Defect that Prevents AIDS :: Biology Gene HIV

Introduction A number of recent studies show overwhelming evidence that there is a genetic factor which presents itself in the human host, and is critical to the ineffectivity of the In Vitro transmission of HIV-1. This genetic factor is an individual defective CKR-5 (also known as "CCR-5") allele containing a 32-base pair deletion in a region of the gene opposite to the second extracellular loop of the receptor. This defect faults the normal expression of the CKR-5 which is the co-receptor for the macrophagic tropic strains of HIV-1. Through a study of 1252 high-risk homosexual men in the Chicago area, indications were that no members of the HIV-infected caucasians were homozygous for the mutation, and the frequency of heterozygotes was 35% lower than in the general population. One percent of the people with Western European decent were found to be homozygous for the defect while about 20% were found to heterozygous. This shows that the 32-base pair deletion of the CKR-5 allele is a very importa nt factor in the HIV-1 transmission and pathogenesis. The 32-base pair deletion and its implications is a new and exciting find in the rhelm of AIDS and HIV research. Every day new findings are being published dealing with the topic. As research progresses, is is possible that one day a genetic cure for this type of HIV infection will be found. Research These findings from experiments conducted in the initial research led to the discovery that HIV-1 needs the coreceptor missing in homozygous individuals to infect CD4+ cells. Finding: CKR-5 transcripts from EU Cells do not encode an active coreceptor. Tests were conducted on human embryonic kidney cells infected with CD4 and CKR-5 expression vectors. The vectors were then derived and rendered inactive instead of producing vectors that monitored the entry of the macrophagic-tropic virus form. Finding: EU CKR-5 RNA contains a 32-base coding sequence deletion. A nucleotide sequence of the EU2, EU3, and a normal donor were analyzed by a set of primers. The 32-base pair deletion was found in the EU2 and EU3 individuals. Finding: A defective CKR-5 is encoded in the genomic DNA and is inherited. The firsts tests conducted were aimed at determining if the deletion was inherited or a mutation. The presence of the CKR-5 allele indicated that the deletion was in the genomic DNA and that it was not sex-linked. Finding: The EU2 and EU3 individuals were homozygous for the CKR-5 deletion. The previous analysis suggested that the deletion was either homozygous or heterozygous.