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Journal of NeuroVirology

, Volume 24, Issue 4, pp 411–419 | Cite as

In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques

  • Sanjeev Gumber
  • Praveen Kumar Amancha
  • Po-Jen Yen
  • Francois Villinger
  • Dana Gabuzda
  • Siddappa N. Byrareddy
Article

Abstract

Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.

Keywords

Macrophage-tropic Rhesus macaques Central nerveous system Myeloid cells Macrophages SIV 

Notes

Acknowledgements

We thank Ms. Stephanie Ehnert and the veterinary/support staff of the Yerkes National Primate Research center for their help in conducting macaque studies.

Funding

This study was supported in part by NIH R01AI113883 & R21AI114415 to SNB. DG was supported by NIH R01 MH 97659. Several antibodies and TZm-bl cells were obtained from NIH AIDS Reagent Reference Program.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13365_2018_628_Fig4_ESM.gif (48 kb)
Supplementary Fig.S1

Frequencies of classical monocytes (CD14+16-), intermediate monocytes (CD14+CD16+), and mDCs (CD3-CD8-CD20-CD14-CD16-HLADR+CD11c+) from CD4+ T cells depleted (top panel) and non-depleted (bottom panel) animals are shown. (TIFF 661 kb) (GIF 47 kb)

13365_2018_628_MOESM1_ESM.tif (661 kb)
High resolution image (TIFF 661 kb)
13365_2018_628_Fig5_ESM.gif (19 kb)
Supplementary Fig.S2:

Area under curve data for the CD14+16- (classical monocytes) is calculated from the longitudinal data shown in supplementary Fig S1A. A) is the data on individual animal and B) is the Mean and SD of both the groups. The sample size is too small to perform statistical analysis for the observed difference between the two groups. (TIFF 103 kb) (GIF 18 kb)

13365_2018_628_MOESM2_ESM.tif (103 kb)
high resolution image (TIFF 103 kb)
13365_2018_628_Fig6_ESM.gif (363 kb)
Supplementary Fig.S3:

IHC staining from representative tissue sections from CD4+ T cells depleted SIVmac251desiv147#C4 infected rhesus macaques (RDn15 & RCb15). Cervical lymph node (A), lung (B), small intestine (C), and mesenteric lymph node (D) showing SIVmac251 p17 (green) and CD68 (Fuchsin-red) labeled cells along with SIV/CD68 colocalization. (TIFF 661 kb) (TIFF 15577 kb) (GIF 362 kb)

13365_2018_628_MOESM3_ESM.tif (15.2 mb)
High resolution image (TIFF 15577 kb)

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Copyright information

© Journal of NeuroVirology, Inc. 2018

Authors and Affiliations

  • Sanjeev Gumber
    • 1
  • Praveen Kumar Amancha
    • 2
  • Po-Jen Yen
    • 3
  • Francois Villinger
    • 2
  • Dana Gabuzda
    • 3
  • Siddappa N. Byrareddy
    • 4
  1. 1.Division of Pathology, Yerkes National Primate Research CenterEmory UniversityAtlantaGeorgia
  2. 2.New Iberia Research CenterUniversity of Louisiana at LafayetteNew IberiaUSA
  3. 3.Department of Cancer Immunology and VirologyDana-Farber Cancer InstituteBostonUSA
  4. 4.Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaUSA

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