Role of the HIV Env C-terminus in infection and replication

• Applicant: Professorin Dr. Jane Valérie Bosch
• Subject Area: Virology
• Term: from 2004 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5434883

In contrast to most other enveloped viruses, the surface glycoproteins of lentiviruses contain very long C-terminal cytoplasmic tails (CTs) which are absolutely required for virus replication in vivo. Despite the long-standing interest of several research groups worldwide it is, however, presently unclear which essential processes are mediated by these regions. Both present applicants have a long-standing interest in processes mediated by the Env protein of human immunodeficiency virus (HIV). In particular, both have been involved in experimental approaches aimed at understanding the roles played by the HIV-Env-CT in virus infection and replication. The group of V. Bosch has been involved in describing the properties of mutated viruses encoding Envs truncated in the CT ot mutated within the membrane anchor region. Most virions, encoding Cterminally truncated Env, exhibit a cell-specific infectivity defect. More recently, the group has identified, and is in the process of characterizing, phenotypic revertants of these variant virions that the HIV-Env-CT, expressed from retroviral vectors as so-called Env-CT mini protein, inhibits HIV infection. The data so far indicate that the restriction lies at an early post-entry step, implying that one function of the Env-CT could be at this stage. We regard these studies to be highly synergistic and have thus joined forces and put together the following comprehensive and interconnected research proposal. In the following, we describe a variety of different approaches, which, collectively, should provide insight into the role(s) played by the CT of HIV-Env in virus infection and replication. The anticipated identification of cellular binding partners of the CT of HIV Env may eventually identify novel targets for anti-HIV therapy.

• DFG Programme: Research Grants