Analysis of dominant HIV quasispecies suggests independent viral evolution within spinal granulomas coinfected with mycobacterium tuberculosis and HIV-1 Subtype C
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Date
Authors
Danaviah, Sivapragashini
De Oliveira, Tulio
Gordon, Michelle
Govender, Shunmugam
Chelule, Paul
Pillay, Sureshnee
Naicker, Thajasvarie
Cassol, Sharon
Ndung'u, Thumbi
Journal Title
Journal ISSN
Volume Title
Publisher
Mary Ann Liebert
Abstract
Extrapulmonary tuberculosis (TB) is a significant public health challenge in South Africa and worldwide,
largely fuelled by the HIV epidemic. In spinal TB, Mycobacteria infect the spinal column without dissemination
to the spinal cord. The immune microenvironment, target cell characteristics, and other evolutionary
forces within granulomas during HIV/TB coinfection are poorly characterized. We investigated whether spinal
TB granulomas represent a sequestered anatomical site where independent HIV evolution occurs, and assessed
the role of macrophages as a target cell for both HIV and mycobacteria. RNA was extracted from plasma and
granulomatous tissue from six antiretroviral-naive HIV-1/spinal TB-coinfected patients, RT-PCR amplified,
and the C2-V5 env segment was cloned and sequenced. Analysis of genetic diversity, phylogeny and coalescence
patterns was performed on clonal sequences. To investigate their role in HIV sequestration, macrophages
and the HIV-1 p24 protein were immune localized and ultrastructural features were studied. Intercompartment
diversity measurements and phylogenetic reconstruction revealed anatomically distinct monophyletic HIV-1
clusters in four of six patients. Genotypic CCR5-tropic variants were predominant (98.9%) with conservation of
putative N-linked glycosylation sites in both compartments. CD68+ reactivity was associated with higher tissue
viral load (r = 1.0; p < 0.01) but not greater intrapatient diversity (r = 0.60; p > 0.05). Ultrastructural imaging
revealed the presence of bacterial and virus-like particles within membrane-bound intracellular compartments
of macrophages. Spinal tuberculosis granulomas may form anatomically discreet sites of divergent viral evolution.
Macrophages in these granulomas harbored both pathogens, suggesting that they may facilitate the
process of viral sequestration within this compartment.
Description
Keywords
Extrapulmonary tuberculosis (TB), Mycobacteria, Spinal tuberculosis, Human immunodeficiency virus (HIV), Mycobacterium tuberculosis (MTB)
Sustainable Development Goals
Citation
Danaviah, S, De Oliveira, T, Gordon, M, Govender, S, Chelule, P, Pillay, S, Naicker, T, Cassol, S & Ndung'u, T 2016, 'Analysis of dominant HIV quasispecies suggests independent viral evolution within spinal granulomas coinfected with mycobacterium tuberculosis and HIV-1 Subtype C', AIDS Research and Human Retroviruses, vol. 32, no. 3, pp. 262-270.