Muggeridge Lab

Major Research Interest:

Herpes simplex virus 2 (HSV-2)

The current focus of the lab is Herpes simplex virus 2 (HSV-2) causes recurrent genital infections and life-threatening neonatal disease. Epstein-Barr virus (EBV) causes infectious mononucleosis and plays an important role in the development of several B cell and epithelial cell cancers. Like other herpesviruses, both have a lipid envelope containing many membrane proteins, and their entry into cells, and for HSV-2 its subsequent spread to adjacent cells, requires membrane fusion. Transient coexpression of HSV-2 membrane proteins gB, gD, gH and gL, or EBV proteins gB, gH and gL, causes cell fusion in the absence of infection, in a process that in many respects mimics fusion between the virus and cell membranes. Three-dimensional structures are known for gB and the gH/gL complex of both viruses, and there is some limited information from mutagenesis studies about which residues lie within functionally important parts of the proteins. The activity of gB in fusion is generally believed to be triggered by an interaction with gH/gL, but the location of the binding sites on either protein is not clear. Determination of the binding site on gB may facilitate the design of drugs able to interfere with the interaction and thus block membrane fusion and virus entry into cells.

Selected Publications

1. Changotra H, Turk SM, Artigues A, Thakur N, Gore M, Muggeridge MI, Hutt-Fletcher LM. 2016. Epstein-Barr virus glycoprotein M can interact with the cellular protein p32 and knockdown of p32 impairs virus. Virology 489:223-232. PMID: 26773383
2. Muggeridge MI. 2012. Glycoprotein B of herpes simplex virus 2 has more than one intracellular conformation and is altered by low pH. J Virol 86:6444-6456. PMID: 22514344
3. Li W, Minova-Foster TJ, Norton DD, Muggeridge MI. 2006. Identification of functional domains in herpes simplex virus 2 glycoprotein B. J Virol 80:3792-3800. PMID: 16571796
4. Muggeridge MI, Grantham ML, Johnson FB. 2004. Identification of syncytial mutations in a clinical isolate of herpes simplex virus 2. Virology 328:244-253. PMID: 15464844
5. Fan ZH, Grantham ML, Smith MS, Anderson EA, Cardelli JA, Muggeridge MI. 2002. Truncation of HSV type 2 glycoprotein B increases its cell surface expression and activity in cell-cell fusion, but these properties are unrelated. J Virol 76:9271-9283. PMID: 12186911
6. Muggeridge MI. 2000. Characterization of cell-cell fusion mediated by herpes simplex virus 2 glycoproteins gB, gD, gH and gL in transfected cells. J Gen Virol 81:2017-2027. PMID: 10900041