Research Projects
Characterization of Host Factors Involved in Virus Infections


Programme(s) to which this project applies:

☒ MPhil/PhD ☑ MRes[Med] ☒ URIS
About the Project

Objective and Significance:

A molecular understanding of host cellular factors involved in virus infections is crucial not only to provide novel insights into pathways hijacked by them, but also for development of effective antimicrobials against such pathogens. Identification of host factors that can be targeted for developing novel anti-viral compounds has the additional benefit of avoiding potential resistance acquired in viruses by mutation and selection.

Research Plan and Methodology:

(a) Role of Aup1 in dengue infection: The complexity of the assembly and release of dengue virus provides a potentially rich source of host targets for interference. Propagation of dengue virus (DENV), West Nile (WNV) and other members of the family appears to involve extensive membrane and lipid remodeling to facilitate virus replication, trafficking, assembly and egress. However, we have been severely limited in our understanding of the role of fundamental biological pathways typically hijacked by flaviviruses. We recently discovered that Aup1 – a lipid droplet associated protein – is heavily upregulated upon dengue infection. Preliminary results suggest that overexpression of Aup1 alone is sufficient to cause increased secretion of dengue virus like particles. Aup1 deficient cells become resistant to dengue infection due to impaired virus-induced autophagy necessary for their replication. The goal of this project is to investigate the functional relevance of lipid droplet associated proteins in the context of dengue infection.

(b) Role of Tsg101 in influenza virus infection: A major response of mammalian cells to viral infections is through upregulation of the interferon type I and II pathways. Viruses in turn implement counter strategies through either the inhibition of IFN response or by activation of proteins that inhibit the function of interferon-stimulated genes (ISGs). The primary antagonist of the host immune response for influenza is NS1. A key interaction documented for NS1 is the dynamics of interaction with the interferon-stimulated gene 15 (ISG15). Upon type-I interferon treatment or virus infection, ISG15 is one of the immediate responders and is expressed in abundance. Based on limited proteomic analysis, the targets of ISGylation have been found to be of the order of a hundred or more genes. We have identified Tsg101 as one of the targets of ISG15 modification. We are currently exploring the functional relevance of this modification during influenza infection and how NS1 counteracts it. We find a strong correlation between the pathogenicity of the virus and the effectiveness of NS1 in preventing ISG15 mediated inhibition of Tsg101 function.

Reference:

Sanyal S, Ashour J, Maruyama T, Altenburg AF, Cragnolini JJ, Bilate A, Avalos AM, GarciaSastre A and Ploegh HL. Type-I interferon imposes a Tsg101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection (2013) Cell Host Microbe 14(5): 510-521

About the Supervisor

Prof R Bruzzone, School of Public Health

Biography
bruzzone@hku.hk

Next Step?

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

  1. your CV,
  2. a brief description of your research interest and experience, and
  3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.