A single mutation may impact infectivity of West Nile and similar viruses

February 16, 2017, Public Library of Science
A photomicrograph revealing some of the histopathologic changes associated with West Nile virus. Credit: A. Wilson; Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc, USCDCP

A mutation that impacts changes in the shape of an essential viral protein may influence the infectivity of West Nile and other viruses in the flavivirus family, according to a new study in PLOS Pathogens.

Flaviviruses are responsible for many diseases of global health importance, including West Nile, dengue, and Zika fevers. However, many of these diseases have no effective vaccines or treatments. Some researchers, including Leslie Goo of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, Maryland, hope that a better understanding of how flaviviruses interact with the immune system's antibodies could enable better prevention and treatment.

In the new study, Goo led a research team in carrying out a series of experiments to test the effects of different in a flavivirus called envelope (E) protein, which plays a major role in infection. Using E protein from West Nile, they identified a mutation called T198F that makes E protein more sensitive to inhibition with antibodies.

E protein is known to change shape in a process known as "viral breathing," which alternately hides and exposes certain parts of the protein. Further experiments revealed that T198F occurs in a part of E protein that regulates viral breathing, resulting in exposure of another, otherwise poorly accessible part of the protein.

The scientists introduced the T198F mutation into different flaviviruses and found that, in West Nile and dengue, but not in Zika, it did indeed increase accessibility of a relatively hidden protein region, making this region more vulnerable to antibodies. When introduced into mice, West Nile virus containing this mutation reduced infectivity and disease severity.

Further research is needed to better understand E protein viral breathing behavior, as well as how it impacts flavivirus infection in mice and, possibly, humans. The resulting knowledge could help pave the way to new vaccines and antiviral drugs.

Explore further: Scientists find clue to why Zika, but not its close relatives, causes birth defects

More information: Goo L, VanBlargan LA, Dowd KA, Diamond MS, Pierson TC (2017) A single mutation in the envelope protein modulates flavivirus antigenicity, stability, and pathogenesis. PLoS Pathog 13(2): e1006178. DOI: 10.1371/journal.ppat.1006178

Related Stories

Scientists find clue to why Zika, but not its close relatives, causes birth defects

February 6, 2017
The most frightening aspect of Zika virus has been its ability to produce severe fetal birth defects during pregnancy, especially microcephaly—a small head.

Lab vaccine shields mice against Zika virus

December 14, 2016
Antibodies drawn from a patient infected with Zika could form the basis of a vaccine against the notorious virus, a new animal study suggests.

Why humans (and not mice) are susceptible to Zika

May 19, 2016
Flaviviruses—such as Zika, dengue, and yellow fever—have emerged as human (and other primate) pathogens because of their ability to specifically overcome our anti-viral defenses. In the case of Zika, researchers at the ...

Recommended for you

Rhesus macaque model offers route to study Zika brain pathology

June 21, 2018
Rhesus macaque monkeys infected in utero with Zika virus develop similar brain pathology to human infants, according to a report by researchers at the California National Primate Research Center and School of Veterinary Medicine ...

Breakthrough treatment for crippling jaw disease created

June 20, 2018
A first-ever tissue implant to safely treat a common jaw defect, known as temporomandibular joint dysfunction, has been successfully tested by UCI-led researchers in a large animal model, according to new findings.

Cell-free DNA profiling informative way to monitor urinary tract infections

June 20, 2018
Using shotgun DNA sequencing, Cornell University researchers have demonstrated a new method for monitoring urinary tract infections (UTIs) that surpasses traditional methods in providing valuable information about the dynamics ...

New flu vaccine only a little better than traditional shot

June 20, 2018
A newer kind of flu vaccine only worked a little bit better in seniors this past winter than traditional shots, the government reported Wednesday.

Blood signature could improve early tuberculosis diagnosis

June 19, 2018
A gene signature in the bloodstream could reveal whether someone is going to develop active tuberculosis (TB) disease months before symptoms begin. Such a signature has now been developed by a team led by the Francis Crick ...

Scientists uncover a factor important for Zika virus host species restriction

June 19, 2018
Princeton University researchers Qiang Ding, Alexander Ploss, and colleagues have identified one of the mechanisms by which Zika virus (ZIKV) circumvents immune control to replicate in human cells. The paper detailing this ...

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.