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Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status

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Abstract

Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection.

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Acknowledgments

The authors thank Paul Foryt and Yi Gao. This work was supported by a National Institutes of Health grant [ABR MH080636].

Conflict of interest

The authors declare no conflicts of interest. This information has not been previously presented.

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Authors and Affiliations

  1. Department of Radiology, Northwestern University, 737 North Michigan Avenue, Suite 1600, Chicago, IL, 60611, USA

    Suyang Li, Christina L. Sammet, Riti Mahadevia & Ann B. Ragin

  2. Center for Advanced Imaging, NorthShore University HealthSystem, 2650 Ridge Avenue, Evanston, IL, 60201, USA

    Ying Wu

  3. Department of Radiology, Pritzker School of Medicine, The University of Chicago, Chicago, IL, 60637, USA

    Ying Wu

  4. Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA, 94118, USA

    Sheila M. Keating

  5. Center for Clinical Research Informatics, NorthShore University Hospital, 2650 Ridge Avenue, Evanston, IL, 60201, USA

    Hongyan Du

  6. Department of Neurology, Northwestern University, 710 North Lake Shore Drive, Chicago, IL, 60611, USA

    Cindy Zadikoff

  7. Division of Neurology, Lurie Children’s Hospital, 2300 Children’s Plaza, Chicago, IL, 60614, USA

    Leon G. Epstein

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  1. Suyang Li
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Correspondence to Ann B. Ragin.

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Li, S., Wu, Y., Keating, S.M. et al. Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status. J. Neurovirol. 19, 452–460 (2013). https://doi.org/10.1007/s13365-013-0197-3

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  • DOI: https://doi.org/10.1007/s13365-013-0197-3

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