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Complement and HIV-I infection/HIV-associated neurocognitive disorders

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Abstract

The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response. Complement, a critical mediator of innate and acquired immunity, plays important roles in defeating many viral infections by the formation of a lytic pore or indirectly by opsonization and recruitment of phagocytes. While the role of complement in the pathogenesis of HIV-1 infection and HAND has been previously recognized for over 15 years, it has been largely underestimated thus far. Complement can be activated through HIV-1 envelope proteins, mannose-binding lectins (MBL), and anti-HIV-1 antibodies. Complement not only fights against HIV-1 infection but also enhances HIV-1 infection. In addition, HIV-1 can hijack complement regulators such as CD59 and CD55 and can utilize these regulators and factor H to escape from complement attack. Normally, complement levels in brain are much lower than plasma levels and there is no or little complement deposition in brain cells. Interestingly, local production and deposition of complement are dramatically increased in HIV-1-infected brain, indicating that complement may contribute to the pathogenesis of HAND. Here, we review the current understanding of the role of complement in HIV-1 infection and HAND, as well as potential therapeutic approaches targeting the complement system for the treatment and eradications of HIV-1 infection.

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Acknowledgments

The authors gratefully acknowledge support from the National Institutes of Health grants NIHR21CA141324 and 1R01CA166144 (to X.B.Q.).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neuroscience, Temple University School of Medicine, Room# 749, 3500 N Broad Street, Philadelphia, PA, 19140, USA

    Fengming Liu, Shen Dai, Jennifer Gordon & Xuebin Qin

  2. Department of Immunology, Shandong University School of Medicine, #44 Wenhua Xi Road, Jinan, Shandong, 250012, People’s Republic of China

    Fengming Liu & Shen Dai

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  1. Fengming Liu
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  2. Shen Dai
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  3. Jennifer Gordon
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  4. Xuebin Qin
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Correspondence to Xuebin Qin.

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Liu, F., Dai, S., Gordon, J. et al. Complement and HIV-I infection/HIV-associated neurocognitive disorders. J. Neurovirol. 20, 184–198 (2014). https://doi.org/10.1007/s13365-014-0243-9

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  • DOI: https://doi.org/10.1007/s13365-014-0243-9

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