Infection of humans with herpes simplex virus type 1 (HSV-1) is common and is either asymptomatic or associated with lib blisters. Macaques are infected with a closely related herpesvirus, termed herpes B virus (Macacine alphaherpesvirus 1). Infected animals develop either no or mild symptoms. In contrast, transmission of herpes B virus to humans is believed to invariably cause encephalitis, which may be lethal in the absence of treatment. However, it is largely unknown why herpes B virus threatens human health while this does not seem to be the case for closely related herpesviruses, including HSV-1. This question is addressed by Dr. Michael Winkler. For this, he is developing plasmid systems which allow production and manipulation of these viruses in vitro. Moreover, he is equipping primate herpesviruses with reporter genes that allow easy detection of infected cells and he is developing cell culture systems that allow a side by side characterization of herpes B virus and related primate herpesviruses.
The interferon (IFN) system is an integral component of innate immunity and an important defense against viral infection. The IFN system contributes to control of HSV-1 infection in humans and is required for latent infection of neurons. Latently infected cells carry the viral genetic information but do not produce infectious viruses. Dr. Winkler is investigating whether herpes B virus is more adept in evading the human IFN system than HSV-1 and whether this precludes latent infection of neurons.
Maschkowitz .G, S. Gärtner, H. Hofmann-Winkler, H. Fickenscher and Winkler M. Interaction of Human Cytomegalovirus Tegument Proteins ppUL35 and ppUL35A with Sorting Nexin 5 Regulates Glycoprotein B (gpUL55) Localization. J Virol. 2018 Apr 13;92(9).
Gerlach T., L. Hensen, T. Matrosovich, J. Bergmann, M. Winkler, C. Peteranderl, HD. Klenk, F. Weber, S. Herold, S. Pöhlmann and M. Matrosovich. pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs. J. Virol. 2017 12;91(11).
Wrensch F., M. Hoffmann, S. Gärtner, I. Nehlmeier, M. Winkler and S. Pöhlmann. Virion Background and Efficiency of Virion Incorporation Determine Susceptibility of Simian Immunodeficiency Virus Env-Driven Viral Entry to Inhibition by IFITM Proteins. J. Virol. 2017 3;91(2). pii: e01488-16.
Winkler M., S. Gärtner, F. Wrensch, M. Krawczak, U. Sauermann and S. Pöhlmann. Rhesus macaque IFITM3 gene polymorphisms and SIV infection. PLoS One 2017 3;12(3):e0172847.
Bogdanow B, H. Weisbach, J. von Einem, S. Straschewski, S. Voigt, M. Winkler, C. Hagemeier and L. Wiebusch. Human cytomegalovirus tegument protein pp150 acts as a cyclin A2-CDK-dependent sensor of the host cell cycle and differentiation state. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17510-5.