Our Research
Herpesviruses are extremely complex viruses. We are just beginning to understand exactly how these pathogens manipulate our immune system to establish lifelong infections. In order to develop new therapies and vaccines, it is first necessary to understand the intimate interplay between herpesviruses and their hosts.
Research in the “Virology and Innate Immunity” group focuses on how herpesviruses are recognized by the innate immune system. In addition, our research analyzes how these viruses so successfully establish lifelong, chronic infections. The question of how herpesviruses circumvent or weaken the defensive line of our innate immune system plays a central role, as this is a requirement for the viruses to successfully establish lifelong infection.
Fundamental research for development of novel therapies
Via millions of years of coevolution, herpesviruses have adapted themselves perfectly to their hosts. They know exactly which switches to pull to weaken certain aspects of the immune response as well as to enhance responses that benefit them. The mechanisms used by herpesviruses to manipulate our immune system are explored in research projects in the “Virology and Innate Immunity” group. One goal of the research group is to identify novel viral proteins that are directly involved in manipulation of immune defenses. These proteins are potential targets for the development of new antiviral therapies. Another focus of our research is the characterisation of the pro- or antiviral role of interferon-stimulated gene products during herpesviral infections and their mechanism of action.
Spotlight: the herpesviruses CMV and KSHV
Research in the “Virology and Innate Immunity” group focuses on two members of the herpesvirus family: human herpesvirus 5, also known as cytomegalovirus (CMV), and human herpesvirus 8, or Kaposi’s sarcoma-associated herpesvirus (KSHV).
CMV is a common pathogen, thought to infect half of the European population. In many healthy individuals, CMV infection is unrecognized - it may cause mild illness or even be completely asymptomatic. However, in patients with weakened immune systems, for example in HIV/AIDS patients and transplant recipients, CMV infection can cause severe complications.
In addition, CMV infection of the mother during pregnancy can lead to infection of the fetus, which can result in permanent damage observed at birth or later in childhood. CMV-induced birth defects include mental handicap, deafness, microcephaly, and/or visual impairment. In fact, CMV infection during pregnancy is the most common cause of non-genetic deafness in children.
To date, there is no vaccine against CMV and there is only a limited selection of antiviral drugs available, which are unfortunately accompanied by serious side effects.
KSHV was first discovered in 1994. Since then, it has been identified as the causative agent of at least three types of cancer:
- a cancer of blood vessels, known as Kaposi’s sarcoma,
- a type of lymphoma, or cancer of white blood cells, known as primary effusion lymphoma,
- a form of lymph node enlargement, known as multicentric Castleman’s disease.
The goal of our research activities is to gain novel insights into the interplay between the herpesviruses CMV and KSHV and their hosts, and thus better understand how these viruses cause illness. These insights are the foundation required to develop innovative, specific therapies against herpesviruses.
Our Research
Herpesviruses are extremely complex viruses. We are just beginning to understand exactly how these pathogens manipulate our immune system to establish lifelong infections. In order to develop new therapies and vaccines, it is first necessary to understand the intimate interplay between herpesviruses and their hosts.
Research in the “Virology and Innate Immunity” group focuses on how herpesviruses are recognized by the innate immune system. In addition, our research analyzes how these viruses so successfully establish lifelong, chronic infections. The question of how herpesviruses circumvent or weaken the defensive line of our innate immune system plays a central role, as this is a requirement for the viruses to successfully establish lifelong infection.
Fundamental research for development of novel therapies
Via millions of years of coevolution, herpesviruses have adapted themselves perfectly to their hosts. They know exactly which switches to pull to weaken certain aspects of the immune response as well as to enhance responses that benefit them. The mechanisms used by herpesviruses to manipulate our immune system are explored in research projects in the “Virology and Innate Immunity” group. One goal of the research group is to identify novel viral proteins that are directly involved in manipulation of immune defenses. These proteins are potential targets for the development of new antiviral therapies. Another focus of our research is the characterisation of the pro- or antiviral role of interferon-stimulated gene products during herpesviral infections and their mechanism of action.
Spotlight: the herpesviruses CMV and KSHV
Research in the “Virology and Innate Immunity” group focuses on two members of the herpesvirus family: human herpesvirus 5, also known as cytomegalovirus (CMV), and human herpesvirus 8, or Kaposi’s sarcoma-associated herpesvirus (KSHV).
CMV is a common pathogen, thought to infect half of the European population. In many healthy individuals, CMV infection is unrecognized - it may cause mild illness or even be completely asymptomatic. However, in patients with weakened immune systems, for example in HIV/AIDS patients and transplant recipients, CMV infection can cause severe complications.
In addition, CMV infection of the mother during pregnancy can lead to infection of the fetus, which can result in permanent damage observed at birth or later in childhood. CMV-induced birth defects include mental handicap, deafness, microcephaly, and/or visual impairment. In fact, CMV infection during pregnancy is the most common cause of non-genetic deafness in children.
To date, there is no vaccine against CMV and there is only a limited selection of antiviral drugs available, which are unfortunately accompanied by serious side effects.
KSHV was first discovered in 1994. Since then, it has been identified as the causative agent of at least three types of cancer:
- a cancer of blood vessels, known as Kaposi’s sarcoma,
- a type of lymphoma, or cancer of white blood cells, known as primary effusion lymphoma,
- a form of lymph node enlargement, known as multicentric Castleman’s disease.
The goal of our research activities is to gain novel insights into the interplay between the herpesviruses CMV and KSHV and their hosts, and thus better understand how these viruses cause illness. These insights are the foundation required to develop innovative, specific therapies against herpesviruses.
Melanie Brinkmann studied biology at the Georg-August University Göttingen and the Humboldt University Berlin in Germany. During her PhD at the Institute of Virology, Hannover Medical School, Germany, she studied how the tumorvirus Kaposi sarcoma-associated herpesvirus (KSHV) manipulates its host. For her postdoctoral time she joined Hidde Ploeghs laboratory at the Whitehead Institute for Biomedical Research, which is affiliated with the Massachusettes Institute of Technology in Cambridge, USA. During these four years she worked on highly specialized sentinels of the innate immune system, so called pattern recognition receptors. These cellular receptors play an essential role for the detection of viral infections.
Since July 2010 Melanie Brinkmann is head of the research group “Virology and Innate Immunity” at the HZI.
She received the PhD Award of the Hannover Medical School (2004), for her postdoctoral work she received the Robert-Koch-Postdoc Award (2007), and in 2016 she was awarded with the Science Award of the Signal Transduction Society.
From 2012 to 2018, Melanie Brinkmann was assistant professor at the Institute of Virology at the Hannover Medical School. Since July 2018 she is professor at the Institute of Genetics at the Technische Universität Braunschweig.
Team
Selected Publications
Günther T, Czech‐Sioli M, Indenbirken D, Robitaille A, Tenhaken P, Exner M, Ottinger M, Fischer N, Grundhoff A, Brinkmann MM.
SARS‐CoV‐2 outbreak investigation in a German meat processing plant
EMBO Mol Med. 2020. e13296 (DOI: 10.15252/emmm.202013296)
Stempel M, Chan B, Brinkmann MM.
Coevolution pays off: Herpesviruses have the license to escape the DNA sensing pathway.
Med Microbiol and Immunol. Aug 2019. 208: 495. (DOI: 10.1007/s00430-019-00582-0)
Stempel M, Chan B, Juranić Lisnić V, Krmpotić A, Hartung J, Paludan SR, Füllbrunn N, Lemmermann NA, Brinkmann MM.
The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling and STING's dual role during MCMV infection.
EMBO J. 2019 Jan 29. pii: e100983. [Epub ahead of print] (DOI: 10.15252/embj.2018100983)
Bussey KA, Lau U, Schumann S, Gallo A, Osbelt L, Stempel M, Arnold C, Wissing J, Gad HH, Hartmann R, Brune W, Jänsch L, Whitehouse A, Brinkmann MM.
The interferon-stimulated gene product oligoadenylate synthetase-like protein enhances replication of Kaposi's sarcoma-associated herpesvirus (KSHV) and interacts with the KSHV ORF20 protein.
PLoS Pathog. 2018 Mar 2;14(3):e1006937. eCollection 2018 Mar. (DOI: 10.1371/journal.ppat.1006937)
Chan B, Gonçalves Magalhães V, Lemmermann NAW, Juranić Lisnić V, Stempel M, Bussey KA, Reimer E, Podlech J, Lienenklaus S, Reddehase MJ, Jonjić S, Brinkmann MM. (2017)
The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.
PLoS Pathog. 2017 May 25;13(5):e1006382. eCollection 2017 May. (DOI:10.1371/journal.ppat.1006382)
A complete list of publications can be found here.
International DEEP-DV Summer School
Further information about the Deep-DV project you can find here.
InfectNET
Further information about the Network of German Female Infectional Researchers you can find here.