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Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B

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Abstract

A defective chemokine motif in the HIV-1 Tat protein has been hypothesized to alter central nervous system cellular trafficking and inflammation, rendering HIV-1 subtype C less neuropathogenic than B. To evaluate this hypothesis, we compared biomarkers of cellular chemotaxis and inflammation in cerebrospinal fluid (CSF) and serum in individuals infected with HIV-1 subtypes B (n = 27) and C (n = 25) from Curitiba, Brazil. None had opportunistic infections. Chemokines (MCP-1, MIP-1α, MIP-1β, RANTES, IP-10) and cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-10) were measured using the multiplex bead suspension array immunoassays or ELISA HD. CSF and serum biomarker concentrations were compared between subtype B and C groups and HIV-positive and HIV-negative subjects (N = 19) using an independent group t test (unadjusted analysis) and linear regression (adjusted analysis), controlling for nadir CD4 and CSF and plasma HIV RNA suppression. CSF levels of cytokines and chemokines were significantly (p < 0.05) elevated in HIV-positive versus HIV-negative participants for 7/13 biomarkers measured, but levels did not differ for subtypes B and C. Serum levels were significantly elevated for 4/13 markers, with no significant differences between subtypes B and C. Although pleocytosis was much more frequent in HIV-positive than in HIV-negative individuals (27 vs. 0 %), subtypes B and C did not differ (32 and 22 %; p = 0.23). We did not find molecular evidence to support the hypothesis that intrathecal chemotaxis and inflammation is less in HIV-1 subtype C than in subtype B. Biomarker changes in CSF were more robust than in serum, suggesting compartmentalization of the immunological response to HIV.

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Acknowledgments

This work was supported by the following grants: National Institute of Health, NIH R21 MH76651 (Ellis, Ronald J; Almeida, Sergio M.), NIH R01 MH83552 (Smith, David M.), S10 RR31646 (Letendre, Scott), K24 MH097673 (Letendre, Scott); University of California, San Diego, Center for AIDS Research (CFAR), an NIH-funded program (P30 AI036214), which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK; Ministério da Ciência e Tecnologia/Conselho Nacional de Desenvolvimento Científico e Tecnológico, MCT/CNPq-Universal 014/2008, Brazil (Almeida, Sergio M.).

The HIV Neurobehavioral Research Center (HNRC) is supported by Center award P30MH062512 from NIMH. The San Diego HIV Neurobehavioral Research Center [HNRC] group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System, and includes the following: Director: Robert K. Heaton, Ph.D., Co-Director: Igor Grant, M.D.; Associate Directors: J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., and Scott Letendre, M.D.; Center Manager: Thomas D. Marcotte, Ph.D.; Jennifer Marquie-Beck, M.P.H.; Melanie Sherman; Neuromedical Component: Ronald J. Ellis, M.D., Ph.D. (P.I.), Scott Letendre, M.D., J. Allen McCutchan, M.D., Brookie Best, Pharm.D., Rachel Schrier, Ph.D., Debra Rosario, M.P.H.; Neurobehavioral Component: Robert K. Heaton, Ph.D. (P.I.), J. Hampton Atkinson, M.D., Steven Paul Woods, Psy.D., Thomas D. Marcotte, Ph.D., Mariana Cherner, Ph.D., David J. Moore, Ph.D., Matthew Dawson; Neuroimaging Component: Christine Fennema-Notestine, Ph.D. (P.I.), Monte S. Buchsbaum, M.D., John Hesselink, M.D., Sarah L. Archibald, M.A., Gregory Brown, Ph.D., Richard Buxton, Ph.D., Anders Dale, Ph.D., Thomas Liu, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Cristian Achim, M.D., Ph.D.; Neurovirology Component: David M. Smith, M.D. (P.I.), Douglas Richman, M.D.; International Component: J. Allen McCutchan, M.D., (P.I.), Mariana Cherner, Ph.D.; Developmental Component: Cristian Achim, M.D., Ph.D.; (P.I.), Stuart Lipton, M.D., Ph.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.), Jennifer Marquie-Beck, M.P.H.; Data Management and Information Systems Unit: Anthony C. Gamst, Ph.D. (P.I.), Clint Cushman; Statistics Unit: Ian Abramson, Ph.D. (P.I.), Florin Vaida, Ph.D. (Co-PI), Reena Deutsch, Ph.D., Anya Umlauf, M.S.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government.

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Authors and Affiliations

  1. Universidade Federal do Paraná, Curitiba, Paraná, Brazil

    Sergio M. de Almeida, Indianara Rotta, Sonia M. Raboni & Clea E. Ribeiro

  2. Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil

    Sergio M. de Almeida & Indianara Rotta

  3. Seção de Virologia, Setor Análises Clínicas, Hospital de Clínicas – UFPR, Rua Padre Camargo, 280, Curitiba, PR, Brazil, 80060-240

    Sergio M. de Almeida

  4. Alzheimer’s Therapeutic Research Institute, University of Southern California, San Diego, CA, USA

    Yanxin Jiang

  5. Chicago Cleaning House, Chicago, IL, USA

    Xiao Li & Scott Letendre

  6. Division of Infectious Diseases, Department of Medicine, University of California, San Diego, CA, USA

    Davey Smith

  7. HIV Neurobehavioral Research Center, University of California, San Diego, San Diego, CA, USA

    Michael Potter & Ronald J. Ellis

  8. Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego, CA, USA

    Florin Vaida

  9. Department of Neurosciences, University of California, San Diego, CA, USA

    Ronald J. Ellis

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  1. Sergio M. de Almeida
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  2. Indianara Rotta
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  3. Yanxin Jiang
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  10. Scott Letendre
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  11. Ronald J. Ellis
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Correspondence to Sergio M. de Almeida.

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de Almeida, S.M., Rotta, I., Jiang, Y. et al. Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B. J. Neurovirol. 22, 715–724 (2016). https://doi.org/10.1007/s13365-016-0437-4

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