Genetic analyses of the promoter region of interleukin-10 gene in different species of monkeys: implications for HIV/AIDS progression.

Abstract

Recently a number of promoter alleles of interleukin-10 (IL-10) have been described in humans that affect the progression of HIV-1. Since infection of different species of monkeys with HIV-1, HIV-2 and SIV result in a widely varying outcome of the disease, we sought to study the nature of IL-10 promoter mutations in three different species of monkeys, namely rhesus, baboon and marmoset. We have identified three novel types of polymorphisms in monkeys that are characterized by insertions, deletions and substitutions besides several single nucleotide polymorphisms. Most interesting results were obtained with rhesus monkeys that lacked the 10-base long deletion in the polymorphic region B and the 12-base substitution in the polymorphic region C identified in marmoset monkeys. It is obvious that mutations of this nature involving insertions, deletions or substitutions of large sequences may potentially change the structure of the chromosome that are likely to affect binding of various transcription factors and consequently levels of transcription. The promoter region studied is highly polymorphic when compared to humans and at several places the changes are unique for a particular species of monkey. These observations may directly impact upon the progression of HIV-1 disease including other diseases/disorders where IL-10 levels have been implicated.