Herpes simplex virus (HSV) infections last a
lifetime. Once a person has been infected, the virus
can remain dormant (latent) for years before
periodically reactivating to cause recurrent
This poorly understood cycle has frustrated
scientists for years.
Now, National Institutes of Health scientists have
identified a set of protein complexes that are
recruited to viral genes and stimulate both initial
infection and reactivation from latency.
Environmental stresses known to regulate these
proteins also induce reactivation.
Globally, the World Health Organization estimates
that 500 million people are infected with HSV-2
while two-thirds of the population are infected with
These viruses cause human diseases ranging from oral
cold sores to genital lesions to serious eye
conditions that can lead to blindness.
In infants, HSV can cause neurological and
Scientists at NIH’s National Institute of Allergy
and Infectious Diseases previously made progress
toward understanding the role of cellular protein
HCF-1 in initiating HSV infection and reactivation.
HCF-1 and associated proteins are recruited to the
viral genome to enable the virus to replicate and
This previous work identified targets for the
development of therapeutics to suppress infection
Their latest work, with collaborators from Princeton
University, Princeton, New Jersey, identifies new
HCF-1 protein complexes that play additional roles
in initiating viral infection and reactivation.
The scientists found they could reactivate latent
HSV in a mouse model using compounds that turn on
components of these HCF-1 protein complexes.
Interestingly, some of these HCF-1-associated
proteins also are involved in HIV reactivation from
The researchers are continuing to investigate the
protein complexes involved in promoting HSV gene
expression, infection, and reactivation from
Identifying these complexes and understanding the
mechanisms by which they function can potentially
reveal additional targets for the development of new
for more information
Cell Host & Microbe
Transcriptional Elongation of HSV Immediate Early
Genes by the Super Elongation Complex Drives Lytic
Infection and Reactivation from Latency
U.S. National Institutes of Health