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Title: Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection
Authors: Mishra, Mamata
Varghese, Rebu K.
Verma, Anjali
Das, Sutanuka
Aguiar, Renato Santana
Tanuri, Amilcar
Mahadevan, Anita
Shankar, Susarla K.
Satishchandra, Parthasarathy
Ranga, Udaykumar
Keywords: Neurosciences
Subtype C
HIV-associated dementia
Proviral load
Clade-Specific Differences
HIV-1-Associated Dementia
Nondemented Patients
Coreceptor Usage
Loop Sequences
Viral Load
Type-1 DNA
RNA Levels
Issue Date: 2015
Publisher: Springer
Citation: Journal of Neurovirology
Mishra, M.; Varghese, R. K.; Verma, A.; Das, S.; Aguiar, R. S.; Tanuri, A.; Mahadevan, A.; Shankar, S. K.; Satishchandra, P.; Ranga, U., Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection. J. Neurovirol. 2015, 21 (4), 399-414.
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.
Description: Restricted access
ISSN: 1355-0284
Appears in Collections:Research Papers (Udaykumar Ranga)

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