Goffinet Lab – Innate immunity and viral evasion

Research Focus

The research group "Innate Immunity and Viral Evasion" is interested in gaining a better understanding of the interplay between host cells and viruses at the cellular and molecular level.

HIV-1, the causative agent of AIDS, remains one of the most devastating viral pathogens worldwide and causes chronic immunodeficiency. Using human target cells of HIV-1, we characterize their ability to sense, with the help of the cellular pattern recognition receptors, an invading HIV-1 infection, and how efficiently this information translates into a functional antiviral state. Vice versa, we identify and elucidate HIV-1-mediated evasion strategies of this cellular innate immunity, which explain why HIV-1 is successfully circumventing cellular defense mechanisms. Furthermore, we investigate the mode of action of cellular restriction factors, focusing on the antiviral proteins 90K and SERINC5, which can reduce the infectivity of HIV-1 particles. Knowledge on these naturally occurring molecular weapons of human cells, and how HIV-1 has evolved to counteract them, could pave new avenues towards antiviral drugs. In addition, we are developing strategies for eradication of latently HIV-1-infected resting T-cells.

We are also investigating the early processes of Chikungunya virus infection and the innate immune responses during the infection. Chikungunya virus is an emerging and rapidly expanding pathogen which causes an acute, self-limiting infection in most cases. A subset of infected persons, however, suffers from chronic joint pain and inflammation, justifying research to develop protective and/or therapeutic options which are completely missing to date. Using both infectious particles and pseudotyped vectors, we aim to study immunological restriction as well as the entry process and replication of the virus.

Team

  • Prof. Dr. rer. nat. Christine Goffinet, Group Leader
  • Julia Kazmierski, MSc: I am investigating cell-intrinsic innate immunity in HIV-1-infected T-cells and try to understand how HIV-1 counteracts these cellular defense mechanisms.
  • Baxolele Mhlekude, PhD: I am investigating antiviral restriction factors with the goal to provide new starting points for the development of antiviral strategies.
  • Fabian Pott, MSc: I am establishing a primary cell model of ex vivo Chikungunya virus infection with the goal to illuminate the in vivo pathogenesis of and the antiviral response to this virus.

Selected Publications

Susceptibility of Chikungunya Virus to Inactivation by Heat and Commercially WHO-Recommended Biocides, Journal of Infectious Diseases, 2018, www.ncbi.nlm.nih.gov/pubmed/29917109

The Antiviral Activity of the Cellular Glycoprotein LGALS3BP/90K is Species-Specific, Journal of Virology, 2018, www.ncbi.nlm.nih.gov/pubmed/29743357

cGAS-mediated innate immunity spreads intercellularly through HIV-1 Env-induced membrane fusion sites, Cell Host & Microbe, 2016, www.ncbi.nlm.nih.gov/pubmed/27736643

90K, an interferon-stimulated gene product, reduces the infectivity of HIV-1, Retrovirology, 2013, www.ncbi.nlm.nih.gov/pubmed/24156545

HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor, Cell Host & Microbe, 2009, www.ncbi.nlm.nih.gov/pubmed/19286137

HIV-susceptible transgenic rats allow rapid preclinical testing of antiviral compounds targeting virus entry or reverse transcription, Proceedings of the National Academy of Sciences USA, 2007, www.ncbi.nlm.nih.gov/pubmed/17209012