Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection

Mishra, Mamata and Varghese, Rebu K and Verma, Anjali and Das, Sutanuka and Aguiar, Renato Santana and Tanuri, Amilcar and Mahadevan, Anita and Shankar, Susarla K and Satishchandra, Parthasarathy and Ranga, Udaykumar (2015) Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection. In: JOURNAL OF NEUROVIROLOGY, 21 (4). pp. 399-414.

PDF Jou_of_Neu_21-4_399_2015.pdf - Published Version Restricted to Registered users only Download (2MB) | Request a copy

Abstract

In India, the low prevalence of HIV-associated dementia (HAD) in the Human immunodeficiency virus type 1 (HIV-1) subtype C infection is quite paradoxical given the high-rate of macrophage infiltration into the brain. Whether the direct viral burden in individual brain compartments could be associated with the variability of the neurologic manifestations is controversial. To understand this paradox, we examined the proviral DNA load in nine different brain regions and three different peripheral tissues derived from ten human subjects at autopsy. Using a highly sensitive TaqMan probe-based real-time PCR, we determined the proviral load in multiple samples processed in parallel from each site. Unlike previously published reports, the present analysis identified uniform proviral distribution among the brain compartments examined without preferential accumulation of the DNA in any one of them. The overall viral DNA burden in the brain tissues was very low, approximately 1 viral integration per 1000 cells or less. In a subset of the tissue samples tested, the HIV DNA mostly existed in a free unintegrated form. The V3-V5 envelope sequences, demonstrated a brain-specific compartmentalization in four of the ten subjects and a phylogenetic overlap between the neural and non-neural compartments in three other subjects. The envelope sequences phylogenetically belonged to subtype C and the majority of them were R5 tropic. To the best of our knowledge, the present study represents the first analysis of the proviral burden in subtype C postmortem human brain tissues. Future studies should determine the presence of the viral antigens, the viral transcripts, and the proviral DNA, in parallel, in different brain compartments to shed more light on the significance of the viral burden on neurologic consequences of HIV infection.

Item Type:	Journal Article
Publication:	JOURNAL OF NEUROVIROLOGY
Publisher:	SPRINGER
Additional Information:	Copy right for this article belongs to the SPRINGER, 233 SPRING ST, NEW YORK, NY 10013 USA
Keywords:	HIV-1; Subtype C; HIV-associated dementia; Proviral load
Department/Centre:	Division of Electrical Sciences > Electronic Systems Engineering (Formerly Centre for Electronic Design & Technology)
Date Deposited:	19 Aug 2015 05:23
Last Modified:	29 Oct 2018 15:33
URI:	http://eprints.iisc.ac.in/id/eprint/52137

Actions (login required)

View Item