Sunday, September 25, 2016

Zika Virus Causes Problems for Monkeys, Too

Zika virus is currently a worldwide concern. Spread by mosquitoes and through sexual contact, the virus has been highlighted in the news since May 2015, when it was first detected in Brazil.i Since then, it has taken the world by storm: as of September 22, 2016, it has affected 47 countries/territories in North and South America, with over 275,000 suspected or confirmed cases in Brazil alone.ii (To view the interactive map, please click here.) With all of the fear and news coverage surrounding the outbreak, researchers are racing to learn more about this critical illness. A new paper, published on September 12, 2016, claims to have some of the answers.
Zika virus infection is often asymptomatic, but for pregnant individuals, the consequences can be devastating. Zika virus is associated with microcephaly (small head) and other fetal malformations.iii In addition, Guillain-Barré Syndrome, a type of autoimmune-induced muscle weakness, has been associated with Zika infection.iii In this research article, Adams Waldorf et al. (2016) primarily investigated the virus’s effects on fetal brain development. For this experiment, the team injected a Cambodian strain of the virus (strain FSS13025, Cambodia 2010) into five locations on the forearms of a pregnant pigtailed macaque monkey (see image of pigtailed macaque below). The monkey was had been pregnant for 119 days, approximately equivalent to 28 weeks of human pregnancy. The fetus was viewed by ultrasound weekly, and cesarean section was performed 43 days later (equivalent to 38 weeks in human pregnancy). The results were simply astonishing.

Within 10 days of the virus injection, the developing fetus began to encounter problems. The fetus showed lesions (damaged areas) on its brain, which evolved differently on the left and right hemispheres. In the left hemisphere, the fetus showed loss of brain volume, and even ventricular collapse (complete destruction of a ventricle, a hollow area within the brain). In the right hemisphere, the lesions simply increased in severity over time. White matter, one of the types of brain tissue consisting mainly of nerve fibers, stopped growing over time, while gray matter, another type of brain tissue consisting mainly of nerve cell bodies, continued to grow. The picture below shows some of this damage, indicated by red arrows (the numbers at the top signify the number of days after injection/the number of days since conception).

After cesarean section, the fetus was autopsied for further investigation. Evidence of the virus was detected in the brain, which showed significant underdevelopment of white matter. Brain lesions were observed throughout. These findings are very similar to reports of Zika virus in human fetuses, as seen by magnetic resonance imaging (MRI) after birth.
As groundbreaking as this study is, there are several flaws in its design. Only a single subject was investigated, and this subject was a pigtail macaque monkey. Meanwhile, a previous study conducted on rhesus macaques failed to produce similar results.iv  Therefore, the result of this pigtail macaque study could be coincidental or unrepresentative of typical Zika effects. Also, this study used five injection sites, giving a very high dose of the virus, which may not be reflective of an ordinary bite from a virus-carrying mosquito.
Future studies should include larger sample sizes, and should include several different types of macaque monkeys or similar species. In addition, future research could explore the mechanism causing the observed symptoms. How does the virus cause damage to the developing fetus? Lastly, more research needs to be conducted to determine if the pigtailed macaque could be a good model on which to test new medications for Zika virus. If pigtailed macaque monkeys respond very similarly to humans, then perhaps potential new vaccines could be tested on them, before the vaccines move to human trials.

Paper: Waldorf, K. M. A., Stencel-Baerenwald, J. E., Kapur, R. P., Studholme, C., Boldenow, E., Vornhagen, J., ... & Armistead, B. (2016). Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate. Nature Medicine.

Other sources:
iBBC News (August 31, 2016). Zika outbreak: What you need to know. Retrieved September 25, 2016, from http://www.bbc.com/news/health-35370848
iiEpidemic Diseases - Zika in the Americas. (September 22, 2016). Retrieved September 25, 2016, from http://ais.paho.org/phip/viz/ed_zika_countrymap.asp
iiiWorld Health Organization. 2016. Zika virus, microcephaly and Guillain-Barré syndrome. World Health Organization, Geneva, Switzerland. Retrieved September 25, 2016 from http://apps.who.int/iris/bitstream/10665/204961/1/zikasitrep_7Apr2016_eng.pdf?ua=1
ivDudley, D. M., Aliota, M. T., Mohr, E. L., Weiler, A. M., Lehrer-Brey, G., Weisgrau, K. L., ... & Gellerup, D. D. (2016). A rhesus macaque model of Asian-lineage Zika virus infection. Nature communications, 7.

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