A research group from the Department of Biochemistry and Molecular Biology of the University of Valencia (UV), in coordination with the National Center for Biotechnology (CNB) of the CSIC, has studied the role of the interactions within the membrane of proteins from viral families Herpesviridae and Poxviridae in the control of programmed cell death. The work, published in Nature Communications, could have implications for the development of treatments for viral infection, as well as the prevention of related cancers.
The results of the finding, led by Dr. Luis Martínez, Ph.D. in the Department of Biochemistry and Molecular Biology, would imply that intra-membrane interactions between virus proteins and the host individual can be used as therapeutic targets for the treatment of some viral infections. An agent that can block such interactions would not only reduce or even inhibit viral replication, but also slow the potential development of cancer associated with such infections.
Cell apoptosis (programmed cell death) is an essential process in multicellular organisms as it contributes to the balance between cell death, proliferation and differentiation, which is relevant for the development and proper functioning of living things. This makes it a highly regulated process involving many components, including the protein family known as Bcl2 (B cell lymphoma 2).
To maximize their growth, viruses in the Herpesviridae and Poxviridae families have evolved mechanisms to modulate cell death in host individuals. Therefore, these viruses have proteins structurally similar to Bcl2 proteins, known as viral Bcl2, that have a transmembrane domain that allows the protein to be introduced into the target membrane to deregulate cell apoptosis.
In this study, we show that viral Bcl2 proteins have a transmembrane domain (TMD) that allows them to be anchored to the mitochondrial membrane. In addition, we have observed that these proteins can interact with each other and with other Bcl2 proteins of hosts through this domain. Our results also indicate that these interactions are key to controlling cell death following an apoptotic stimulus such as a viral infection. “
Dr. Luis Martínez, Ph.D., Department of Biochemistry and Molecular Biology
García-Murria, AJ, et al. (2020) Viral Bcl2s’ transmembrane domain interacts with host Bcl2 proteins to control cellular apoptosis. Nature. doi.org/10.1038/s41467-020-19881-9.