NIAID Now | July 13, 2020
Zika virus particles (red) shown in African green monkey kidney cells.
Two new Zika virus studies provide greater detail about how the virus spreads in hosts, with one study offering new therapeutic targets and the other explaining how certain cells protect a fetus from infection. The unrelated studies are from research groups at Rocky Mountain Laboratories (RML), part of the National Institute of Allergy and Infectious Diseases in Hamilton, Montana.
Recall that in 2015-16 Zika virus was a dominant global public health story because the virus—while typically mild to those infected—could result in serious birth defects in the developing children of pregnant women. Aedes aegypti mosquitoes can carry the virus and spread it to people when they bite for a blood meal. In 2016 there were more than 5,000 Zika virus disease cases reported in the United States according to the Centers for Disease Control and Prevention; nearly all were from travelers returning from affected areas. Since then, according to the World Health Organization, cases have been at low levels though the virus remains a concern. There is no vaccine or treatment for disease caused by Zika virus.
Several research groups are working to further understand the virus in order to develop treatments and preventions against Zika, including those at RML led by Dr. Karin Peterson and Dr. Sonja Best.
In a study published June 3 in The Journal of Immunology, Dr. Peterson’s group found that maternal virus-fighting white blood cells (macrophages and monocytes, collectively called myeloid cells) in the placenta of mice infected with a human strain of Zika virus prevented the virus from entering the developing pup, thus protecting it from infection. They noticed that the number of myeloid cells increases in the placenta during Zika virus infection. When they treated the mice in their study to decrease the numbers of myeloid cells in the placenta, Zika virus infection increased in the developing pups. This suggests the myeloid cells suppress the ability of the virus to cross the placenta, something the group plans to pursue in its studies.
The work from Dr. Best’s group, published July 8 in Nature with colleagues from the University of Texas Medical Branch and elsewhere, shows how Zika virus might target its growth in the testes and central nervous system (CNS) of some people. Using a mouse model of disease, they found that the protein that enables virus entry into cells, called the envelope, can hijack and use a host protein, TRIM7, to modify its outer surface and help the virus infect host cells. The levels of TRIM7 are highest in cells of the brain and reproductive tissues. This means the virus could use its interaction with TRIM7 for easy, efficient infection of CNS and testes. The scientists now are pursuing whether a treatment that stops the modification of envelope by TRIM7 would effectively prevent Zika virus infection.
References:
C Winkler et al. Placental myeloid cells protect against Zika virus vertical transmission in a Rag1-deficient mouse model. The Journal of Immunology (2020).
M Giraldo et al. Flavivirus envelope protein ubiquitination drives virus entry and pathogenesis. Nature (2020).