Editors' ChoiceHIV

Antiviral Traps: HIV Avoids a Sticky Situation

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Science Translational Medicine  01 Aug 2012:
Vol. 4, Issue 145, pp. 145ec138
DOI: 10.1126/scitranslmed.3004665

The mainstay of HIV therapy is to suppress the microbe by using powerful antiretroviral medications; however, preventing or eradicating the virus is a major goal. Enhancing host adaptive cellular and humoral immunity is one strategy to combat HIV, but despite tremendous efforts, it has so far proved ineffective. Now, Saitoh et al. report an unexpected discovery. They show that the host innate immune system is able to ensnare and eliminate HIV, but the wily virus has found a way to evade this trap.

Neutrophil extracellular traps (NETs) are specialized DNA structures embedded with histones and antimicrobial enzymes that are released by neutrophils to capture microbial invaders. NETs entrap bacteria and fungal pathogens, but it is not yet clear whether they are also effective against viral pathogens. In their new study, Saitoh et al. induce the release of NETs from human neutrophils in vitro using a chemical stimulant. They directly visualize HIV sticking to the NET DNA and histone proteins using superresolution-structured illumination microscopy. NETs had antiviral activity resulting in HIV inactivation partly through the action of the NET components myeloperoxidase and α-defensin. Interestingly, HIV nucleic acids directly triggered NET production by activating Toll-like receptors 7 and 8 expressed by neutrophils. Remarkably, these NETs inhibited the ability of HIV to infect CD4+ T lymphocytes, confirming their antiviral potential.

Unfortunately, HIV quickly disarms this innate immune cell trap by stimulating the DC-SIGN receptor on dendritic cells, causing release of a NET-suppressive factor. Further investigation revealed that this factor was interleukin-10, which blocks cell signaling downstream of Toll-like receptors 7 and 8. This new study demonstrates the importance of the innate immune system in fighting viral infections and highlights the possibility of eliminating HIV by using neutrophil DNA traps. Yet HIV continues to elude our natural host defense mechanisms as well as our targeted therapies. At least now we understand one way in which HIV escapes the traps laid by the host innate immune system. This new information may enable us to devise NET-based therapies and new ways to counteract the NET suppressive effects of HIV.

T. Saitoh et al., Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe 12, 109–116 (2012). [PubMed]

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