Secreted Herpes Simplex Virus-2 Glycoprotein G Modifies NGF-TrkA Signaling to Attract Free Nerve Endings to the Site of Infection

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Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) establish latency in peripheral sensory ganglia, where they remain for the lifetime of the infected individual. Understanding the mechanisms that allow these viruses to colonize the nervous system will permit devising antiviral strategies. We show that HSV-2 glycoprotein G (SgG2) binds to and increases the function of nerve growth factor (NGF), a neurotrophin expressed in the skin and mucosa essential for axonal growth and neuronal survival. This constitutes the first description, to our knowledge, of a human pathogen with the ability to augment neurotrophic factor function. The enhancement in NGF activity results in an increase in axonal growth of neurons expressing the receptor for NGF. These results were obtained in vitro, ex vivo and in the infected mouse, suggesting that this effect may permit a more efficient infection of NGF dependent free nerve endings by HSV-2. Absence of a similar function for HSV-1 gG may indicate a preference for the infection of particular subsets of neurons by these viruses. These results shed light on the modulation of neurotrophic factors by relevant human pathogens and on the mechanisms of colonization of the nervous system by HSV.

Vyšlo v časopise: Secreted Herpes Simplex Virus-2 Glycoprotein G Modifies NGF-TrkA Signaling to Attract Free Nerve Endings to the Site of Infection. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004571
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004571

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