Prof Greg Towers
Our work aims to understand the molecular details of host virus interactions. We focus on human immunodeficiency virus type 1, the cause of AIDS in humans, but we also study other retroviruses as well as herpes viruses such as HSV-1, human cytomegalovirus and Kaposi’s sarcoma herpes virus and adenoviruses.We study host virus interactions because we believe that the new knowledge we find will be valuable in many ways. For example, we expect that a more detailed understanding of host virus interactions will help us to drug viral infection experimentally and therapeutically. We are developing novel inhibitors of viral infection that manipulate viruses’ ability to hide from innate immune pattern recognition receptors. We also aim to use our understanding of innate immune control of HIV-1 to develop novel gene therapy based approaches to treat HIV-1 infection.
We believe that viruses are very good cell biologists and by working out how they interact with their hosts we will discover new understanding of host cell processes. We also believe that one cannot truly appreciate the relationship between host and virus without a sound understanding of evolution. This is best illustrated by Lee Van Valen’s Red Queen hypothesis, which suggests that host and pathogen are locked in a genetic conflict in which both host and virus are obliged to continually evolve with each alternately gaining and losing the advantage.
We also study host virus interactions because it is a very competitive and well-funded area of research that is really good fun to work in.
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Dr Jane Rasaiyaah
I am interested in the role of the innate immune system in anti-HIV host defence and pathogenesis of viral diseases. In this context, HIV-1 infects macrophages, key sentinel cells of the immune system, which are well equipped to detect pathogens and mediate innate immune responses.
I am interested in understanding
how HIV-1 evades detection by the sensors of the innate immune system and how
host-virus interactions govern protection. I am particularly interested in the
role of host cofactors for HIV-1 infection in these processes.
Dr Laura Hilditch
Following entry into the cell, HIV-1 must undergo reverse transcription of the viral genome, timely loss of the capsid protein, and traverse the nuclear pore. Host proteins Nup358, TNPO3 and CPSF6 have recently been identified as integral to the completion of these processes, but the precise molecular mechanisms are not yet fully understood.
I am interested in understanding how these proteins act as cofactors for lentiviruses and understanding the molecular details of their interactions. I believe that this work will not only further our understanding of HIV-1 evolution but will also aid the design of vaccines novel antivirals and the use of model viruses.
Dr Choon Ping Tan (Tan)
I am interested in the mechanisms of viral restriction by the family of tripartite-motif containing proteins (TRIMs). Members of this family bear the tripartite motif comprising RING, B-box and Coiled Coil domains. In the case of TRIM5a specific structures within the incoming virus capsid are recognised by the C terminal PRYSPRY motif, which then recruits proteasome activity to effect degradation and restriction of infection.
Our group has worked on interaction between TRIM5α and a specific subclass of retroviruses and has gained mechanistic insight into the mechanism of viral degradation. I aim to extend these findings to the TRIM21 protein, which recognises antibody-bound viruses via its PRYSPRY domain. TRIM21 recognition and destruction of invading pathogen tagged with antibody appears similar in mechanism to TRIM5a and highlights the versatility of TRIM antiviral activity.
CPSF6 is a host protein with a role in 3’ mRNA processing and splicing, which has been shown to interact with HIV-1’s capsid protein. I am interested in the role of CPSF6 in the early stages of HIV-1 infection. We believe that CPSF6 is a cofactor for HIV-1 infection, and that HIV-1 has evolved to interact with CPSF6 in order to be appropriately targeted to the nuclear pore complex.
I am to determine the mechanism by which CPSF6 carries out this role, as well as how it cooperates with other host cofactors in the nuclear import pathway of HIV-1.
Dr Christoffer Van Tulleken
The non-homologous end joining pathway (NHEJ) is known to circularize linear HIV DNA after reverse transcription. Prevention of this process by reduction of any of the components leads to apoptosis presumably due to a pro apoptotic signal activated by the DNA free ends. Because the circles formed are not productive, circularization may be a defensive act for the host but may also help the virus evade pattern recognition.
Previous experiments considering a role for the NHEJ pathway in HIV infection have been performed in cells which are unlikely to be competent for effective innate pattern recognition and so I am seeking to investigate the effect on HIV replication and innate immune stimulation of the NHEJ in T-Cell lines and human primary cells using siRNA knock downs and microarrays.
am studying the ability of Interferon to inhibit HIV-1 replication. I
am considering which restriction factors may play a role in the ability
of interferon treatment to suppress HIV-1 replication in primary human
monocyte derived macrophages.
Page last modified on 12 feb 14 16:01 by Jane Lorna Elizabeth Turner