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. 2018 Feb;24(1):62-74.
doi: 10.1007/s13365-017-0594-0. Epub 2017 Nov 27.

Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy

Stefanie Perez  1   2 , Ann-Marie Johnson  1 , Shi-Hua Xiang  3 , Jian Li  4 , Brian T Foley  5 , Lara Doyle-Meyers  1 , Antonito Panganiban  1   6 , Amitinder Kaur  1   6 , Ronald S Veazey  1   7 , Yuntao Wu  8 , Binhua Ling  9   10
Affiliations

Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy

Stefanie Perez et al. J Neurovirol. 2018 Feb.

Abstract

Persistence of HIV-1 reservoirs in the central nervous system (CNS) is an obstacle to cure strategies. However, little is known about residual viral distribution, viral replication levels, and genetic diversity in different brain regions of HIV-infected individuals on combination antiretroviral therapy (cART). Because myeloid cells particularly microglia are likely major reservoirs in the brain, and more microglia exist in white matter than gray matter in a human brain, we hypothesized the major viral reservoirs in the brain are the white matter reflected by higher levels of viral DNA. To address the issue, we used the Chinese rhesus macaque (ChRM) model of SIV infection, and treated 11 SIVmac251-infected animals including long-term nonprogressors with cART for up to 24 weeks. SIV reservoirs were assessed by SIV DNA levels in 16 specific regions of the brain and 4 regions of spinal cord. We found relatively high frequencies of SIV in basal ganglia and brain stem compared to other regions. cART-receiving animals had significantly lower SIV DNA levels in the gray matter than white matter. Moreover, a shortened envelope gp120 with 21 nucleotide deletions and guanine-to-adenine hypermutations were observed. These results demonstrate that SIV enters the CNS in SIV-infected ChRM with a major reservoir in the white matter after cART; the SIV/ChRM/cART is an appropriate model for studying HIV CNS reservoirs and testing new eradication strategies. Further, examining multiple regions of the CNS may be needed when assessing whether an agent is successful in reducing the size of SIV reservoirs in the CNS.

Keywords: Antiretroviral therapy; Central nervous system; Human immunodeficiency virus; Reservoir; Rhesus macaque; Simian immunodeficiency virus.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Correlations between SIV RNA loads in plasma and cerebrospinal fluid (CSF) in untreated SIV-infected Chinese rhesus macaques.
Figure 2
Figure 2
Comparison of levels of SIV gag DNA between gray matter and white matter in the group of cART-treated (A) and untreated Chinese rhesus macaques (ChRM) (B), and levels of SIV gag DNA in gray matter between groups of untreated and cART-treated ChRM (C) and in white matter (D). Solid diamond, SIV gag DNA viral load in gray matter of ChRM on ART; solid square, SIV gag DNA viral load in white matter of ChRM on ART; Open diamond, SIV gag DNA viral load in gray matter of untreated ChRM; Open square, SIV gag DNA viral load in white matter of untreated ChRM; ***: p < 0.0001, N. S., no significance.
Figure 3
Figure 3
Phylogenetic analysis of SIV envelope gp120 sequences of variants isolated from gray and white matter of different regions of the brain in 2 SIV-infected typical progressors without cART (TP1 and TP2) and 2 SIV-infected ChRM on cART (DT1 and DT2). Each sequence was named as animal name-label number of the brain followed with the left (L) or right (R)-gray or white with more than one sequence if followed with a number, for instance, TP2-20L-G1 (the 2nd typical progressor animal-left temporal lobe-gray matter sequence 1) represents sequence 1 that was isolated from the gray matter of left temporal lobe in the 2nd typical progressor animal. The tree scale bar indicates the number of substitutions per site.
Figure 4
Figure 4
Amino acid sequence comparison of SIV envelope V1 loop and V4 loop of SIVmac239, SIVmac251, variants from each sample group. TP1, test animal 1 (representative sequence); TP2, test animal 2; DT1, drug treated animal 1; DT2, drug treated animal 2. HQ series and HM series, GenBank sequences; and KC strains, parental strains. Dots represent amino acid identity with reference strain SIVmac239; dashes represent deletions.
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References

    1. Ballabh P, Braun A, Nedergaard M. Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res. 2004;56:117–24. - PubMed
    1. Becker JT, Maruca V, Kingsley LA, Sanders JM, Alger JR, Barker PB, Goodkin K, Martin E, Miller EN, Ragin A, Sacktor N, Selnes O, Multicenter ACS. Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology. 2012;54:113–21. - PMC - PubMed
    1. Brew BJ, Robertson K, Wright EJ, Churchill M, Crowe SM, Cysique LA, Deeks S, Garcia JV, Gelman B, Gray LR, Johnson T, Joseph J, Margolis DM, Mankowski JL, Spencer B. HIV eradication symposium: will the brain be left behind? J Neurovirol. 2015;21:322–34. - PMC - PubMed
    1. Churchill M, Nath A. Where does HIV hide? A focus on the central nervous system. Curr Opin HIV AIDS. 2013;8:165–9. - PMC - PubMed
    1. Churchill MJ, Deeks SG, Margolis DM, Siliciano RF, Swanstrom R. HIV reservoirs: what, where and how to target them. Nat Rev Microbiol. 2016;14:55–60. - PubMed

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