Research News
New research on herpes simplex virus has implications for treating ocular herpes
The National Institute of Allergies & Infectious Diseases has awarded funding for an innovative research study to determine how the herpes simplex virus enters into human cells at the molecular level and how it then spreads from cell to cell.
“A better understanding of virus-cell interactions during virus entry can lead to new strategies for preventing and treating herpes simplex infections, including ocular herpes” says Deepak Shukla , PhD and director of the Ocular Virology Laboratory.
Shukla, assistant professor in the Department of Ophthalmology & Visual Sciences, is principal investigator of the study, entitled “Molecular Mechanism of HSV Entry and Spread.” Funded through 2010, the study advances Shukla’s breakthrough research in virus entry and spread, which uncovered a novel entry receptor for herpes simplex virus-1 (HSV-1).
HSV infections are very common, and, once acquired, they are for life. While symptoms generally are as benign as an occasional cold sore, for some – especially those with inadequate access to health care, compromised immune systems, or living in underdeveloped regions of the world – HSV can cause recurrent, incurable and even deadly symptoms.
Ocular herpes, a form of the infection of particular interest to the Shukla lab, is caused when HSV-1 infects the eye. The infection produces a painful sore and can cause inflammation of the cornea. The less severe forms of ocular herpes include blepharatis, conjunctivitis, and epithelial keratitis. The severest form is stromal keratitis, which causes scarring of the cornea and can lead to loss of vision and blindness.
Viral entry is a complex process in which tiny, specialized “spikes” on proteins in the virus find receptors on the surface of a cell. There are different proteins as well as different receptors, generating a slew of possible binding combinations for virus entry. The Shukla lab uses genetics, molecular biology, biochemistry, and cell biology to identify these viral and cellular mediators of entry to decipher their precise roles in the entry process.
The newly funded study will focus on one particular entry receptor for HSV-1, called 3-O-sulfated heparin sulfate. 3-OS-HS offers binding sites for an HSV-1 protein spike called envelope glycoprotein D (gD-1). The study will determine the molecular structure of this binding between 3-OS-HS and gD-1 and will then evaluate the role of 3-OS HS in naturally susceptible cells. Finally, the study will identify the molecules that could be manipulated to block HSV infection using a powerful new technology called RNA interference. RNA interference “silences” the interactions of targeted molecules and is the basis of gene therapy.
In 2004, Shukla received a multi-year award from Research to Prevent Blindness, Inc., the world’s leading voluntary organization supporting eye research, for his ocular virology research.
