Spatiotemporal dynamics of simian immunodeficiency virus brain infection in CD8+ lymphocyte-depleted rhesus macaques with neuroAIDS.

J Gen Virol 2014 Dec 9;95(Pt 12):2784-95. Epub 2014 Sep 9.

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA

Despite the success of combined antiretroviral therapy in controlling viral replication in human immunodeficiency virus (HIV)-infected individuals, HIV-associated neurocognitive disorders, commonly referred to as neuroAIDS, remain a frequent and poorly understood complication. Infection of CD8(+) lymphocyte-depleted rhesus macaques with the SIVmac251 viral swarm is a well-established rapid disease model of neuroAIDS that has provided critical insight into HIV-1-associated neurocognitive disorder onset and progression. However, no studies so far have characterized in depth the relationship between intra-host viral evolution and pathogenesis in this model. Simian immunodeficiency virus (SIV) env gp120 sequences were obtained from six infected animals. Sequences were sampled longitudinally from several lymphoid and non-lymphoid tissues, including individual lobes within the brain at necropsy, for four macaques; two animals were sacrificed at 21 days post-infection (p.i.) to evaluate early viral seeding of the brain. Bayesian phylodynamic and phylogeographic analyses of the sequence data were used to ascertain viral population dynamics and gene flow between peripheral and brain tissues, respectively. A steady increase in viral effective population size, with a peak occurring at ~50-80 days p.i., was observed across all longitudinally monitored macaques. Phylogeographic analysis indicated continual viral seeding of the brain from several peripheral tissues throughout infection, with the last migration event before terminal illness occurring in all macaques from cells within the bone marrow. The results strongly supported the role of infected bone marrow cells in HIV/SIV neuropathogenesis. In addition, our work demonstrated the applicability of Bayesian phylogeography to intra-host studies in order to assess the interplay between viral evolution and pathogenesis.

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http://dx.doi.org/10.1099/vir.0.070318-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233634PMC
December 2014
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References

(Supplied by CrossRef)

Current neurology and neuroscience reports 2013

Alter et al.
The Journal of Immunology 2007

American Journal Of Pathology 2010

Annamalai et al.
2010

Autissier et al.
Journal of immunological methods 2010

Molecular Biology and Evolution 2012

Bello et al.
2012

Bissel et al.
Journal of neuroimmunology 2006

Burdo et al.
2010

Burdo et al.
American Journal Of Pathology 2012

Burudi et al.
Advances in virus research 2001

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