Herpes simplex 1 virus, the microscopic pathogen notoriously remembered for its production of painful and unappealing cold sores, has long evaded complete treatment. "Once this virus enters the body, it never leaves,” said biologist Jue Chen, PhD, from The Rockefeller University, leader of a new study investigating this pesky invader. Using a technique known as cryo-electron microscopy in the study recently published in
Nature, Chen and her team observed how herpes avoids the primary recognition system of the immune system to thrive ubiquitously in the human body.
A protein called TAP for “the transporter associated with antigen processing” works intracellularly to bring antigenic particles from the cytosol to the endoplasmic reticulum (
Physiology). From the endoplasmic reticulum, compounds called major histocompatibility complex (MHC) I molecules take the antigens for displaying on the cell surface, notifying lymphocytes called cytotoxic T cells of a viral presence within the cell. The images Chen and her team obtained from their study using cryo-electron microscopy showed herpes inhibiting TAP activity, subsequently preventing the host cell from warning the immune system of the herpes presence.
First, herpes prevents TAP from binding to viral particles for transport. Then, herpes makes the transporter “stuck in this conformation.”
"We haven't been able to figure out how to block these transporters ourselves," Chen said, "so we are learning how it's done from viruses, which we hope will teach us some strategies for inhibition."
Initially it may seem that a treatment for herpes is as simple as manipulating TAP to counter or avoid the effect from herpes. However, TAP is universally present in many cells that need it for defense against viruses other than herpes, so the treatment would have to be extremely specific for TAP in cells with herpes virus only. However, the discoveries made in this new study provide insight into treating other viral diseases.
Source:
The Rockefeller University
