Human herpes virus
Infectious diseases
This research aims to give answers to a key aspect of herpes virus biology – namely, reactivation from being latent. The study will importantly also provide the intellectual framework for developing new effective therapies and inhibitors against herpes virus reactivation.
The highly prevalent, neurotropic α-herpes viruses HSV-1, HSV-2 and VZV remain a major concern in health care, both clinically and economically. The pathologies associated with them include genital herpes, infectious blindness, post-herpetic neuralgia and herpes encephalitis and meningitis. Infected individuals carry the virus for life, since latent virus cannot be eliminated from infected neurons, and it is this virus reactivation from latency that is the cause of considerable morbidity.
Research on herpes virus latency was so far largely restricted to the virus itself, due to the scarcity of suitable tools to study the complex system of the host cell and the limited availability of human neurons for infection experiments. However, the entire virus life cycle is a fine balance between the virus on the one hand and the host cell on the other. At the earliest stages of HSV and CMV infection, cellular proteins are recruited to incoming viral genomes to repress viral gene expression. Cells depleted for these cellular repressors enhance virus replication and reduce the ability of the virus to enter latency.
The aim of Dr Glass’s research is to study the role of cellular proteins in neuronal establishment and maintenance of, and reactivation from α-herpes virus latency. Research in this area has been hindered by the lack of a robust system to study infection in neurons.
Dr Glass will develop a system for differentiation of human neurons from pluripotent stem cells to study neuronal virus-cell interaction, and establish protocols for latent infection studies in these stem cell-derived neurons. She has already established new and efficient lentiviral tools to manipulate and analyse the host cell proteins and their mutant variants, which will provide her with the mechanistic insight into the mode of action of cellular proteins involved in neuronal latency.
It is hoped that Dr Glass’ research will elucidate a key aspect of herpes virus biology, but importantly will provide the intellectual framework for developing new effective therapies and inhibitors against herpes virus reactivation.
Infectious Diseases – Human Herpes Virus
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Why there is a need to fund new research
Infections by the human herpes viruses, herpes simplex virus-1 (HSV-1) and varicella zoster virus (VZV), causing common cold sores and chicken pox respectively, are among the most common childhood infections. Although they usually cause mild disease, very rarely, infections can be life threatening. One such rare but serious complication is a brain infection known as encephalitis.
Following chickenpox, VZV remains dormant in the nerves for the lifetime of the person. In about 25% of people, VZV becomes active again, travelling down the nerves to cause the painful skin rash known as shingles. Acute shingles rash can be debilitating and is characterised by significant pain which can last for weeks or months, even after the skin rash has healed. If the pain persists for longer than 3 months after the rash has healed is termed post herpetic neuralgia (PHN). Shingles and PHN gets worse in older individuals and in people whose immune systems do not work properly. Importantly the currently available drugs for treating shingles and PHN are suboptimal and although there is a vaccine which prevents shingles and PHN, it only works in 50-65% of subjects.
More research is needed to address these debilitating and sometimes life threatening comilocaiotn sof herpes virus infection and we were able to provide support thanks to a generous leagacy from Catherine in memory of her mother who suffered from shingles.