Scientists advance understanding of herpesvirus infection

April 12, 2017, NIH/National Institute of Allergy and Infectious Diseases
The left image shows typical HSV reactivation (red) from latency in neurons. On the right, viral reactivation is stimulated by compounds that activate the HCF-1 binding partners. Credit: NIAID

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 disease. This poorly understood cycle has frustrated scientists for years. Now, National Institutes of Health (NIH) 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 one-half billion people are infected with HSV-2 while two-thirds of the population are infected with HSV-1. 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 developmental problems. People infected with HSV also have an enhanced risk of acquiring or transmitting (HIV).

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 spread. This previous work identified targets for the development of therapeutics to suppress infection and reactivation.

Their latest work, with collaborators from Princeton University, 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 latency.

The researchers are continuing to investigate the protein complexes involved in promoting HSV gene expression, infection, and reactivation from latency. Identifying these complexes and understanding the mechanisms by which they function can potentially reveal additional targets for the development of new therapeutics.

Explore further: HBV reactivation seen with DAA treatment of chronic hep C

More information: Roberto Alfonso-Dunn et al, Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency, Cell Host & Microbe (2017). DOI: 10.1016/j.chom.2017.03.007

Related Stories

HBV reactivation seen with DAA treatment of chronic hep C

March 13, 2017
(HealthDay)—For patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs), hepatitis B virus (HBV) reactivation may occur in those with current HBV infection, according to a study published online ...

Scientists describe new herpes treatment strategy

December 3, 2014
Scientists have developed a novel treatment approach for persistent viral infections such as herpes.

Stress wakes up sleeping herpes viruses – but how?

February 24, 2016
Hiding their DNA genome inside the nuclei of the infected cells, the herpes viruses establish a lifelong infection in humans. Poorly defined stress conditions are known to wake up these parasites from their latent phase and ...

Short-course tocilizumab may up hep B reactivation in RA

February 13, 2017
(HealthDay)—For patients with rheumatoid arthritis (RA), one to three doses of tocilizumab may increase the risk of hepatitis B virus (HBV) reactivation, according to a study published online Feb. 3 in the International ...

Designed drug candidate significantly reduces HIV reactivation rate

July 8, 2015
HIV-infected patients remain on antiretroviral therapy for life because the virus survives over the long-term in infected dormant cells. Interruption of current types of antiretroviral therapy results in a rebound of the ...

Nanoparticle exposure can awaken dormant viruses in the lungs

January 16, 2017
Nanoparticles from combustion engines can activate viruses that are dormant in in lung tissue cells. This is the result of a study by researchers of Helmholtz Zentrum München, a partner in the German Center for Lung Research ...

Recommended for you

A versatile vaccine that can protect mice from emerging tick-borne viruses

December 18, 2018
A group of researchers led by Michael Diamond of Washington University School of Medicine in St. Louis have developed a vaccine that is effective in mice against Powassan virus, an emerging tick-borne virus that can cause ...

How cholera bacteria make people so sick

December 18, 2018
The enormous adaptability of the cholera bacterium explains why it is able to claim so many victims. Professor Ariane Briegel from the Leiden Institute of Biology has now discovered that this adaptability is due to rapid ...

Green leafy vegetables may prevent liver steatosis

December 17, 2018
A larger portion of green leafy vegetables in the diet may reduce the risk of developing liver steatosis, or fatty liver. In a study published in PNAS researchers from Karolinska Institutet in Sweden show how a larger intake ...

Discovery of novel mechanisms that cause migraines

December 17, 2018
Researchers at CNRS, Université Côte d'Azur and Inserm have demonstrated a new mechanism related to the onset of migraine. They found how a mutation that causes dysfunction in a protein which inhibits neuronal electrical ...

RNA processing and antiviral immunity

December 14, 2018
The RIG-I like receptors (RLRs) are intracellular enzyme sentries that detect viral infection and initiate a first line of antiviral defense. The cellular molecules that activate RLRs in vivo are not clear.

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.