The biology of Zika virus

Learn about the basic biology, origins, life cycle, and symptoms of Zika virus.

Introduction

You may have heard about Zika virus in the news. Because of Zika’s recent spread in the Americas, many people want to understand more about this virus.
In this article, we’ll take a look at Zika from a biological standpoint. First, we’ll examine the structure, life cycle, and transmission mode of Zika virus, seeing how it infects cells. Then, we’ll look at the effects of Zika on humans, as well as the prospects for controlling and managing the virus.

What is Zika virus?

Zika belongs to a group of viruses called the flaviviruses, which includes dengue, West Nile, and yellow fever1^1. Flaviviruses are tiny structures made up of protein, RNA (a molecule related to DNA), and a lipid membrane. Each viral particle consists of a single-stranded RNA genome tucked inside a protein shell called a capsid, surrounded by an external sphere of membrane known as the envelope2^2. You can see Zika virus particles in the microcope image below right, where they appear as small, dark spheres. One particle is marked with an arrow.
Left, schematic of a Zika virus particle in cross-section and from an exterior view. The virus consists of an RNA molecule, a surrounding protein capsid, and a membrane envelope around the capsid. The envelope contains many proteins that cover the majority of the virus particle's surface.
Right, transmission electron micrograph of Zika virus particles. The particles are visible as small spheres with a dark core and a lighter rim.
_Image credit: left, modified from "Zika virus: Virion," by ViralZone, Swiss Institute of Bioinformatics (CC BY-NC 4.0); right, "Zika virus," by C. Goldsmith, CDC Public Health Image Library (public domain)._
A defining characteristic of viruses is that they cannot reproduce on their own. Instead, they must infect host cells and “reprogram” them to become virus-producing factories. Zika virus is no exception. It cannot replicate by itself, but can infect and replicate inside of the cells of several species, including humans, monkeys, and mosquitoes3^3. Although we don't know which cell types Zika targets in the human body, studies with cultured cells (cells grown in a dish) show that Zika can infect a variety of immune cells found in human skin4^4.

Where did Zika come from?

Zika is not a new virus. It was first isolated from a monkey in the Zika forest of Uganda in 1947, and the first human case was reported in 19545^5. A few additional cases were reported in Africa in the following years, and, starting at the end of the 1960s, in equatorial Asia as well. No serious health complications or outbreaks were documented during this period, and blood tests for antibodies against Zika suggested that people in the affected areas were widely exposed to the virus6^6. For these reasons, Zika was classified as a benign, sporadically occurring virus5^5.
In 2007, the first documented outbreak of Zika took place, on Yap Island in Micronesia. In this outbreak, it was estimated that over 70% of the island's population above the age of 3 was infected with the virus5^5. Although no serious complications or hospitalizations were reported, an outbreak on this scale was unprecedented, as the total number of reported Zika cases to that point had been less than 15. A lack of previous exposure to Zika may have made the population of Yap Island more susceptible to outbreak than populations in the virus's normal range5^5.
In 2013 and 2014, another Zika outbreak occurred, in French Polynesia and the surrounding islands. During this outbreak, health authorities noticed an increased frequency of neurological disorders, including Guillain-Barré syndrome (which causes temporary paralysis), as well as nervous system and brain abnormalities in infants5,7^{5,7}.
The first locally acquired cases of Zika in the Americas were reported in Brazil in May of 2015. Since then, the presence of Zika has been reported in many countries throughout South and Central America. The strains of Zika virus currently found in the Americas are closely related to those from the French Polynesia outbreak, suggesting that the virus may have reached Brazil from French Polynesia 8,9^{8,9}.

How is Zika transmitted?

The primary mode of Zika transmission is through mosquitoes in the genus Aedes. In this regard, Zika is similar to related flaviviruses such as dengue, yellow fever, and West Nile virus. When a mosquito eats a blood meal from a person infected with Zika, the virus can infect the cells of the mosquito. After the mosquito’s infection has developed (usually after a period of about a week and a half), its saliva will contain viral particles10^{10}. When it bites another human to obtain a blood meal, the viral particles can be transmitted to the human, who may contract Zika.
Photograph of Aedes albopictus mosquito.
_Image credit: "Aedes albopictus," by James Gathany, in CDC Public Health Information Library (public domain)._
Although this transmission pathway is by far the most common for Zika virus, other modes of transmission are also possible. For instance, a pregnant woman who contracts Zika may transmit the virus to her growing fetus, or to the baby during birth. There have also been a few documented cases of Zika transmission through sexual contact or through blood transfusions from a Zika-infected donor11,12^{11,12}.

How does Zika infect cells?

Once Zika virus particles are in the human body, they must enter individual cells in order to replicate and make more viruses. Cell entry is possible because a Zika virus particle carries specific proteins on its outer envelope that interact with receptor proteins on human cells. When the viral proteins bind to cell receptors, they “trick” the cells into taking up the viral particle13^{13}.
_Image modified from "Zika virus: Genome, by ViralZone, Swiss Institute of Bioinformatics (CC BY-NC 4.0)._
Inside the cell, the RNA genome of the virus is released into the cytoplasm, or fluid-filled main compartment, of the cell. There, the RNA molecule is “read” (translated) by enzymes in the cell to make a long protein, which is chopped up into a number of smaller proteins (see image at left). Some of these proteins are the structural components needed to make new viral particles, such as capsid and envelope proteins. Other viral proteins copy and process the RNA genome13,14^{13, 14}.
Viral proteins and copies of the RNA genome assemble at the surface of the endoplasmic reticulum (ER), a membrane compartment that’s part of the cell’s export system. New viral particles bud off into the interior of the ER, taking a small patch of ER membrane along with them. This "stolen" membrane will form the viral envelope. The particles then travel through another structure, the Golgi apparatus, where they undergo more processing before release at the cell surface13,14^{13,14}. Released viral particles can infect other cells, continuing the infection cycle.
Diagram based on "The flavivirus life cycle," by Ted Pierson 15^{15}.

What are the symptoms and effects of Zika?

In most cases, the symptoms of Zika infection are very mild. According to the CDC, only 1 in 5 people infected with Zika will get sick at all, and typical symptoms may include rash, fever, conjunctivitis (irritation of the eyes), and joint pain16^{16}. These symptoms generally resolve, and most people do not experience any lasting effects from Zika.
Pregnant women and their unborn fetuses are at higher risk for harmful effects from Zika17^{17}. Specifically, there is a link between Zika infection during pregnancy and a condition called microcephaly (small head) in newborns. Microcephaly may involve neurological problems or developmental delays, but these effects vary greatly from person to person18^{18}. Health authorities are encouraging women who are (or might become) pregnant to take steps to avoid Zika exposure19^{19}.
In a very small fraction of cases, Zika may be linked with neurological problems, such as Guillain-Barré syndrome. Guillain-Barré syndrome is an autoimmune condition that causes paralysis, which is usually temporary (lasting for weeks or a few months in most cases). An increased frequency of Guillain-Barré syndrome has been reported in areas with active Zika infections, but researchers are still investigating whether there is a causal connection20^{20}.

What can be done about Zika?

In the short term, health authorities have recommended that people protect themselves from Zika by avoiding exposure to mosquitos in areas where the virus is active. For people in high-risk groups, such as pregnant women, this might mean postponing travel to areas known to harbor Zika virus21^{21}. For others who live in areas where Zika is active, avoiding exposure might mean remaining indoors, using mosquito repellents and mosquito nets, and removing sources of standing water (which provide a breeding ground for mosquitoes)22^{22}.
In the longer term, a vaccine against Zika could provide more durable protection. Encouragingly, a vaccine against dengue, a flavivirus related to Zika, was recently approved for use in Brazil. This vaccine was built off an inactive version of yellow fever, another related flavivirus, and it’s possible that a similar strategy could be used for a Zika vaccine23^{23}. Recently, promising initial results in mice were reported for one Zika vaccine candidate24^{24}. However, many more tests will be needed to establish whether this and other potential vaccines are safe and effective in humans.
This article is licensed under a CC BY-NC-SA 4.0 license.

Works cited:

  1. Hayes, E. B. (2009). Zika virus outside Africa. Emerging Infectious Diseases, 15(9). http://dx.doi.org/10.3201/eid1509.090442.
  2. Flavivirus. (n.d.). In ViralZone. Retrieved from http://viralzone.expasy.org/all_by_protein/24.html.
  3. Centers for Disease Control and Prevention. (n.d.). Zika: Natural host range. In Arbovirus catalog. Retrieved from https://wwwn.cdc.gov/arbocat/VirusDetails.aspx?ID=536&SID=7.
  4. Hamel, R., Dejarnac, O., Wichit, S., Ekchariyawat, P., Neyret, A., Luplertlop, N., Perera-Lecoin, M., Surasombatpattana, P., Talignani, L., Thomas, F., Cao-Lormeau, V.-M., Choumet, V., Briant, L., Desprès, P., Amara, A., Yssel, H., and Missé, D. (2015). Biology of Zika virus infection in human skin cells. J. Virol., 89(17), 8880-8896. http://dx.doi.org/10.1128/JVI.00354-15.
  5. Kindhauser, M. K., Allen, T., Frank, V., Santhana, R., and Dye, C. (2016, February 09). Zika: The origin and spread of a mosquito-borne virus. In Bulletin of the World Health Organization. http://dx.doi.org/10.2471/BLT.16.171082.
  6. Fagbami, A. H. (1979). Zika virus infections in Nigeria: Virological and seroepidemiological investigations in Oyo State. Journal of Hygiene, 83(2), 213-219. http://dx.doi.org/10.1017/S0022172400025997.
  7. European Center for Disease Prevention and Control. (2015, November 24). Rapid risk assessment: Microcephaly in Brazil potentially linked to the Zika virus epidemic. In Publications. Retrieved from http://ecdc.europa.eu/en/publications/Publications/zika-microcephaly-Brazil-rapid-risk-assessment-Nov-2015.pdf.
  8. Enfissi, A., Codrington, J., Roosblad, J., Kazanji, M., and Rousset, D. (2016). Zika virus genome from the Americas. The Lancet, 387(10015), 227-228. http://dx.doi.org/10.1016/S0140-6736(16)00003-9.
  9. Musso, D. (2015). Zika virus transmission from French Polynesia to Brazil. Emerg. Infect. Dis., 12(10), 1887. http://dx.doi.org/10.3201/eid2110.151125.
  10. Hayes, E. B. (2009). Zika virus outside Africa. Emerg. Infect. Dis., 15(9). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819875/
  11. Centers for Disease Control and Prevention. (2016, February 24). Transmission & risks. In Zika virus. Retrieved from http://www.cdc.gov/zika/transmission/.
  12. Reuters. (2016, February 4). Brazil reports Zika infection from blood transfusions. In Life. Retrieved from http://www.reuters.com/article/us-health-zika-brazil-blood-idUSKCN0VD22N.
  13. Zika virus (strain Mr 766). (n.d.) In ViralZone. Retrieved from http://viralzone.expasy.org/all_by_protein/6756.html.
  14. Bollati, M., Alvarez, K., Assenberg, R., Baronti, C., Canard, B., Cook, S., Coutard, B., Decroly, E., de Laballerie, X., Gould, E. A., Grard, G., Grimes, J. M., Hilgenfeld, R., Jansson, A. M., Malet, H., Mancini, E. J., Mastrangelo, E., Mattevi, A., Milani, M., Moureau, G., Neyts, J., Owens, R. J., Ren, J., Selisko, B., Speroni, S., Steuber, H., Stuart, D. I., Unge, T., and Bolognesi, M. (2010). Structure and functionality in flavivirus NS-proteins: Perspectives for drug design. Antiviral Res., 87(2), 125-148. http://dx.doi.org/10.1016/j.antiviral.2009.11.009.
  15. Centers for Disease Control and Prevention. (2016, February 23). Symptoms, diagnosis, & treatment. In Zika virus. Retrieved from http://www.cdc.gov/zika/symptoms/index.html.
  16. Pierson, T. C. (2012, November 2). The flavivirus lifecycle. In Labs at NIAID. Retrieved from https://www.niaid.nih.gov/research/ted-c-pierson-phd
  17. Centers for Disease Control and Prevention. (2016, April 13). CDC concludes Zika causes microcephaly and other birth defects. In CDC newsroom. Retrieved from http://www.cdc.gov/media/releases/2016/s0413-zika-microcephaly.html.
  18. Centers for Disease Control and Prevention. (2016, February 12). Facts about microcephaly. In Birth defects. Retrieved from http://www.cdc.gov/ncbddd/birthdefects/microcephaly.html.
  19. Centers for Disease Control and Prevention. (2016, February 22). Questions and answers: Zika virus infection (Zika) and pregnancy. In Zika virus. Retrieved from http://www.cdc.gov/zika/pregnancy/question-answers.html.
  20. Preidt, R. (2016, January 27). CDC broadens Zika virus travel alert for pregnant women. In MedlinePlus. Retrieved from https://www.nlm.nih.gov/medlineplus/news/fullstory_156896.html.
  21. Centers for DIsease Control and Prevention. (2016, February 8). Guillain-Barré syndrome Q & A. In Zika virus. Retrieved from http://www.cdc.gov/zika/qa/gbs-qa.html.
  22. World Health Organization. (2016). Zika virus. In Media centre. Retrieved from http://www.who.int/mediacentre/factsheets/zika/en/.
  23. Kruger, R. P. (2016). Zika virus on the move. Cell, 164(4), 585, 587. http://dx.doi.org/10.1016/j.cell.2016.01.040.
  24. Geggel, L. (2016, February 18). Zika virus vaccine shows promising start in mice. In Livescience. Retrieved from http://www.livescience.com/53764-zika-vaccine-works-in-mice.html.

Additional references:

2013-2014 Zika virus outbreaks in Oceania. (2016, February 25). Retrieved February 25, 2016 from Wikipedia: https://en.wikipedia.org/wiki/2013%E2%80%932014_Zika_virus_outbreaks_in_Oceania.
Bleijs, D. A. (2016). Transmission. In Zika virus net. Retrieved from http://www.zikavirusnet.com/transmission.html.
Coombs, C. (2015, February 10). The Zika virus's family tree. In The Atlantic. Retrieved from http://www.theatlantic.com/health/archive/2016/02/zika-yellow-fever-flaviviruses/462171/.
Flavivirus. (2016, February 19). Retrieved from https://en.wikipedia.org/wiki/Flavivirus.
Heiz, F. X. and Stiasny, K. (2012). Flaviviruses and flavivirus vaccines. Vaccine, 30, 4301-4306. http://dx.doi.org/10.1016/j.vaccine.2011.09.114.
Lindenbach, B. (2012). Lifecycle of the Flaviviridae. In Lindenbach lab. Retrieved from http://www.lindenbachlab.org.
Lodish, H., Berk, A., Zipursky, S. L., Matsudaira, P., Baltimore, D., and Darnell, J. (2000). VIruses: Structure, function, and uses. In _Molecular cell biology (4th ed., section 6.3). New York, NY: W. H. Freeman. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK21523/.
Lyons, S. (2016, January 29). Zika virus: What do we know about it, and how can it be contained? In Hub. Retrieved from http://hub.jhu.edu/2016/01/29/zika-virus-public-health-expert.
McNeil, D. G., Saint Louis, C., and St. Fleur, N. (2016, February 24). Short answers to hard questions about Zika virus. In The New York Times: Health. Retrieved from http://www.nytimes.com/interactive/2016/health/what-is-zika-virus.html?_r=1.
Samarasekera, U. and Triunfol, M. (2016). Concern over Zika virus grips the world. The Lancet, 387(10018), 521-524. http://dx.doi.org/10.1016/S0140-6736(16)00257-9.
Vogel, G., Cohen, J., and Enserink, M. (2016, January 29). Zika virus: Your questions answered. In Science: Latest news. Retrieved from http://www.sciencemag.org/news/2016/01/zika-virus-your-questions-answered.
World Health Organization. (2016). The history of Zika virus. In Emergencies. Retrieved from http://www.who.int/emergencies/zika-virus/timeline/en/.
Zika virus. (2016, February 15). Retrieved February 25, 2016 from MicrobeWiki: https://microbewiki.kenyon.edu/index.php/Zika_virus.
Note: This article does not provide medical advice and is for informational purposes only. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on Khan Academy.
Last updated: May 10, 2016
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