Genetic and Functional Characterization of the LTR of HIV-1 Subtypes A and C Circulating in India

Abstract

Genetic analysis of HIV-1 sequences circulating in different parts of India have shown that the predominant proportion of HIV-1 subtypes circulating in India is type C and a small fraction are subtypes A, B, E, and CRFs. We sequenced the HIV-1 LTR promoter region of seven subtype C and five subtype A isolates obtained from two major cities in India. Sequence analysis of the complete promoter and TAR regions revealed conserved subtype-specific variability in several major binding sites. Three NF-kappaB sites were present in all subtype C isolates and two isolates contained an insertion in the MFNLP. The transcriptional activity of one of these isolates may have been hindered due to this insertion. Despite the apparent variability between the LTRs we did not observe any significant difference in the transcriptional activity between subtype C and subtype A. To our knowledge, this is the first study characterizing the genetic structure and functional attributes of subtype A LTRs from India.

Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus

“…Target specificity of the CRISPR/Cas system is very high and a single mutation can disrupt targeting20, meaning that some provirus may escape from this genome-editing machinery if mutations arise in target sequences. However, given that the TAR region is relatively conserved and there is little variation among HIV-1 subtypes21, it could still be an appropriate target for the elimination of latently infected provirus.…”

Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells

“…3). The LTR-R region contains the TAR sequence that is relatively conserved among the HIV-1 subtypes, which could serve as a common target site for anti-viral disruptions 17,34,35 . This consequence matches the fact that LTR serves as a critical and universal element for lentivirus expressional regulations by the transcriptional machinery from both virus-encoded proteins and the host cells during the HIV infections 36,37 .…”

Genetic and functional characterization of human immunodeficiency virus type 1 VprC variants from north India: presence of unique recombinants with mosaic genomes from B, C and D subtypes within the open reading frame of Vpr

“…We recently reported subtype B-and C-specific differences in Vpr-mediated cell cycle progression (Bano et al, 2007a) and in their ability to activate the HIV-1 LTR promoter and cause apoptosis (Bano et al, 2007b). Although genetic variations among several HIV-1 genes such as nef, env and ltr have been reported from different regions of India (Jere et al, 2004;Rodriguez et al, 2007;Bhanja et al, 2007), we provide data on the genetic and functional analysis of Vpr genes from the Punjab/Haryana region of north India, which show the involvement of other subtypes in infections in this region.…”