Lab-created Zika Virus Clone Could Speed Vaccine, Treatment

May 17th, 2016

By Gary Evans, AHC Media Senior Staff Writer

Hoping to find points of attack for vaccines and therapies, researchers have constructed a genetic clone of the Zika virus, which is causing an epidemic of mosquito-borne disease in the Americas.

The recently published study concludes that the Zika clone provides a platform to research virus transmission, disease pathogenesis, and to develop countermeasures, note the authors, a team of researchers at the University of Texas Medical Branch at Galveston. The clone Zika virus they created is infectious, can be transmitted by the primary vector -- Aedes aegypti mosquitoes -- and caused illness and death in research mice.

The explosion of Zika virus in the Americas has raised questions about viral mutation and a host of other issues. In addition to vaccine development and treatment, the clonal research model could shed light on several theories about Zika. The researchers, specifically address the following five hypotheses and possible research approaches with mice in this excerpt from the paper:

1. Zika virus (ZIKV) has undergone adaptive evolution that enhanced mosquito transmission, leading to rapid virus spread and an increased number of human infections. This hypothesis could be tested by comparisons of mosquito infectivity of the older ZIKV strains with recent isolates, followed by using the reverse genetic system to test the effects of recent mutations on mosquito transmission. This mechanism was responsible for the emergence of Chikungunya virus, in which a series of mutations in the viral envelope genes enhanced viral transmission by A. albopictus through increased infection of epithelial cells in the midgut.
2. The Asian lineage of ZIKV has adapted to generate higher viremia in humans, leading to enhanced cross-placental infection and microcephaly. This hypothesis could be tested by engineering adaptive mutations from the recent isolates into the infectious cDNA clone, generating mutant viruses, and quantifying the mutational effect on viral virulence in the A129/AG129 mouse and on microcephaly development.
3. Stochastic [random probability] introduction of ZIKV into a population (in the Pacific and Americas) lacking herd immunity led to greater susceptibility to ZIKV infection and efficient mosquito transmission. Seroprevalence and its correlation with ZIKV transmission and outbreak frequency need to be established to address this hypothesis.
4. Previous infection with dengue virus (DENV) may exacerbate ZIKV disease severity because the two viruses share high amino acids identity and extensive antibody cross-reactivity. This could be tested in the AG129 mouse because this mouse is susceptible to both DENV and ZIKV infections.
5. Human genetic predisposition may account for the severe disease outcomes. Any viral infection is modulated by proviral and antiviral host factors. The interaction between viral and host factors determines the efficiency of infection, pathogenicity, transmission, and epidemic potential. Therefore, variations of critical host factor(s) among infected individuals may contribute to different disease severity.

For much more information on Zika, be sure to check out the June issue of Hospital Employee Health, which is dedicated exclusively to the virus outbreak. For the latest from AHC Media on Zika, be sure to visit reliasmedia.com/Zika.