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

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dc.contributor.author Mishra, Mamata
dc.contributor.author Varghese, Rebu K.
dc.contributor.author Verma, Anjali
dc.contributor.author Das, Sutanuka
dc.contributor.author Aguiar, Renato Santana
dc.contributor.author Tanuri, Amilcar
dc.contributor.author Mahadevan, Anita
dc.contributor.author Shankar, Susarla K.
dc.contributor.author Satishchandra, Parthasarathy
dc.contributor.author Ranga, Udaykumar
dc.date.accessioned 2017-01-04T09:07:02Z
dc.date.available 2017-01-04T09:07:02Z
dc.date.issued 2015
dc.identifier.citation Journal of Neurovirology en_US
dc.identifier.citation 21 en_US
dc.identifier.citation 4 en_US
dc.identifier.citation 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. en_US
dc.identifier.issn 1355-0284
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/2000
dc.description Restricted access en_US
dc.description.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. en_US
dc.description.uri 1538-2443 en_US
dc.description.uri http://dx.doi.org/10.1007/s13365-015-0328-0 en_US
dc.language.iso English en_US
dc.publisher Springer en_US
dc.rights ?Springer, 2015 en_US
dc.subject Neurosciences en_US
dc.subject Virology en_US
dc.subject HIV-1 en_US
dc.subject Subtype C en_US
dc.subject HIV-associated dementia en_US
dc.subject Proviral load en_US
dc.subject Human-Immunodeficiency-Virus en_US
dc.subject Clade-Specific Differences en_US
dc.subject HIV-1-Associated Dementia en_US
dc.subject Nondemented Patients en_US
dc.subject Coreceptor Usage en_US
dc.subject Loop Sequences en_US
dc.subject Viral Load en_US
dc.subject Type-1 DNA en_US
dc.subject RNA Levels en_US
dc.subject Brain en_US
dc.title Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection en_US
dc.type Article en_US


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