Zika virus (ZIKV) was first identified in monkeys in Uganda in 1947. Later, in 1952, it was also found in humans in Uganda and Tanzania. Yet it was only in 2007 that the first Zika outbreak was reported, and the disease only became known worldwide in 2016, during a second outbreak that affected the Americas.
Zika is a positive single-stranded RNA enveloped flavivirus that belongs to the Flaviviridae family and is closely related to the dengue virus, yellow fever virus, and other viruses of the same group that cause well-known diseases throughout the world. The most common route of infection is through a mosquito bite, with the virus being deposited in the human dermis and epidermis. Once in contact with human cells, virus entry is mediated by its envelope protein through endocytosis. After cell infection and multiplication, the virus is released and can be transmitted to non-human primates, other humans (through blood, sex, and pregnancy), or another mosquito that later bites the infected person. After the mosquito bite, the virus multiplies inside the mosquito cells and can be found in its saliva after 8 to 12 days. Once in the mosquito’s saliva, Zika can be transmitted to other humans through the mosquito bite and subsequently virus infection of skin cells, where the cycle starts again.
Zika virus symptoms are usually mild and similar to common flu symptoms, including fever, rash on the skin, headache, joint pain, conjunctivitis, and muscle pain. In rare cases, Zika infection can cause Guillain-Barré syndrome, an autoimmune disease that affects the nervous system. The main and worst consequence of Zika virus infection is related to pregnant women and their foetuses. The virus can cause the foetus to be born with microcephaly and congenital Zika syndrome, which affect future development and cause multiple health issues in the child. Because of that, it is important that pregnant women or people trying to conceive avoid travelling to places with possible Zika outbreaks and transmission. There are three main routes by which the virus can be transmitted. The first and most important is through the bite of infected Aedes aegypt and Aedes albopictus mosquitos. The second is vertical transmission through pregnancy, and the third is through sex with an infected person.
The same mosquito transmitting Zika virus is also responsible for transmitting viruses such as dengue and chikungunya viruses, and therefore controlling the mosquito population can play a major role in the prevention and control of these diseases. Aedes aegypti and Aedes albopictus, the main Zika virus vectors, breed in clean stagnant water, like tree holes, flower pots, and tires that accumulate rainwater, as well as wastewater and sewage. In endemic areas, governments try to educate the population on the importance of disposing of stagnant water that may accumulate in their outdoor and indoor spaces. On the contrary, the use of insecticides has been shown to be effective only for a limited period of time, after which both the mosquito and the virus inevitably bounce back.
Currently, there are no known treatments or vaccines against Zika virus, making prevention especially important. Yet many Zika virus vaccines are in development and may become available to the public in the future, especially in endemic areas and for people travelling to these areas. Different types of vaccines are being studied, such as nucleic-acid vaccines, live attenuated vaccines, virus-like particle vaccines, and others. Some of these vaccines are reaching the preclinical and clinical trial stages.
An important characteristic of Zika’s immunological response is the potential for cross-reactivity between Zika (ZIKV), Dengue (DENV), and other Flaviviruses. Since these viruses share common structural and genetic characteristics, the immune response developed against one may cross-react with others. While cross-reactivity is generally considered a good thing, for certain viruses including flaviviruses it can in fact be harmful to the individual. In a scenario where the person was previously infected by DENV and then later infected with ZIKV, studies have described how the poorly neutralizing antibodies generated during the first infection can exacerbate the subsequent infection, in a phenomenon well described for DENV infection called Antibody Dependent Enhancement (ADE). This is one possible explanation for the more damaging ZIKV infections in DENV endemic places. ADE and other immunological complications remain major obstacles in the development of vaccines for both DENV and ZIKV.
ZIKV infections have reduced considerably in recent years, making it harder to perform efficacy vaccine trials in target populations. Nevertheless, it is important to continue studying this virus and developing candidate drug treatments and vaccines to be best prepared when the next outbreak arrives.
At VRS, we offer a range of tests to study the antiviral properties of compounds and antibodies against Zika virus. Contact us to learn more about these tests and how we can help advance your project!
References:
Agrelli A, de Moura RR, Crovella S, Brandão LAC. ZIKA virus entry mechanisms in human cells. Infect Genet Evol. 2019 Apr;69:22-29. doi: 10.1016/j.meegid.2019.01.018. Epub 2019 Jan 15. PMID: 30658214.
Du, S., Liu, Y., Liu, J. et al. Aedes mosquitoes acquire and transmit Zika virus by breeding in contaminated aquatic environments. Nat Commun 10, 1324 (2019). https://doi.org/10.1038/s41467-019-09256-0
Hamel R, Dejarnac O, Wichit S, et al. Biology of Zika Virus Infection in Human Skin Cells. J Virol. 2015;89(17):8880-8896. doi:10.1128/JVI.00354-15
Dussupt, V., Sankhala, R., Gromowski, G., Donofrio, G., De La Barrera, R., Larocca, R., Zaky, W., Mendez-Rivera, L., Choe, M., Davidson, E., McCracken, M., Brien, J., Abbink, P., Bai, H., Bryan, A., Bias, C., Berry, I., Botero, N., Cook, T., Doria-Rose, N., Escuer, A., Frimpong, J., Geretz, A., Hernandez, M., Hollidge, B., Jian, N., Kabra, K., Leggat, D., Liu, J., Pinto, A., Rutvisuttinunt, W., Setliff, I., Tran, U., Townsley, S., Doranz, B., Rolland, M., McDermott, A., Georgiev, I., Thomas, R., Robb, M., Eckels, K., Barranco, E., Koren, M., Smith, D., Jarman, R., George, S., Stephenson, K., Barouch, D., Modjarrad, K., Michael, N., Joyce, M. and Krebs, S., 2020. Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor. Nature Medicine, 26(2), pp.228-235.
Pattnaik A, Sahoo BR, Pattnaik AK. Current Status of Zika Virus Vaccines: Successes and Challenges. Vaccines (Basel). 2020;8(2):266. Published 2020 May 31. doi:10.3390/vaccines8020266
Blog by Thais Fuscaldi Reboucas
Edited by Reckon Better Scientific Editing
