The rapid spread of Zika virus through the Americas, together with the association of infection with microcephaly and Guillain-Barré syndrome, propelled a somewhat unknown virus onto numerous front pages. The WGS Biology Discussion Group (BDG) recently discussed some of the background for its first podcast to this flavivirus but a little more background may help set the context of what is going to be an intriguing story for months to come.
Zika virus was first identified in 1947 in a sentinel monkey that was being used to monitor for the presence of yellow fever virus (another flavivirus) in the Zika Forest of Uganda. At this time cell lines were not available for studying viruses, so serum from the febrile monkey was inoculated intracerebrally into mice. All the mice became sick, and the virus isolated from their brains was called Zika virus. The same virus was subsequently isolated from Aedes africanus mosquitoes in the Zika forest.
Serological studies done in the 1950s showed that humans carried antibodies against Zika virus, and the virus was isolated from humans in Nigeria in 1968. Subsequent serological studies revealed evidence of infection in other African countries, including Uganda, Tanzania, Egypt, Central African Republic, Sierra Leone, and Gabon, as well as Asia (India, Malaysia, Philippines, Thailand, Vietnam, Indonesia).
Zika virus moved outside of Africa and Asia in 2007 and 2013 with outbreaks in Yap Island and French Polynesia, respectively. The first cases in the Americas were detected in Brazil in May 2015. The virus circulating in Brazil is an Asian genotype, possibly imported during the World Cup of 2014. As of this writing Zika virus has spread to 23 countries in the Americas.
Zika virus is a member of the flavivirus family, which also includes yellow fever virus, dengue virus, Japanese encephalitis virus, and West Nile virus. The genome is a ~10.8 kilobase, positive strand RNA enclosed in a capsid and surrounded by a membrane. The envelope (E) glycoprotein, embedded in the membrane, allows attachment of the virus particle to the host cell receptor to initiate infection. As for other flaviviruses, antibodies against the E glycoprotein are likely important for protection against infection.
Zika virus is transmitted among humans by mosquito bites. The virus has been found in various mosquitoes of the Aedes genus, including Aedes africanus, Aedes apicoargenteus, Aedes leuteocephalus, Aedes aegypti, Aedes vitattus, and Aedes furcifer.Aedes albopictus was identified as the primary vector for Zika virus transmission in the Gabon outbreak of 2007. Whether there are non-human reservoirs for Zika virus has not been established.
Signs and Symptoms
Most individuals infected with Zika virus experience mild or no symptoms. About 25% of infected people develop symptoms 2-10 days after infection, including rash, fever, joint pain, red eyes, and headache. Recovery is usually complete and fatalities are rare.
Two conditions associated with Zika virus infection have made the outbreak potentially more serious. The first is development of Guillain-Barré syndrome, which is a progressive muscle weakness due to damage of the peripheral nervous system. The association of Guillain-Barré was first noted in French Polynesia during a 2013 outbreak.
Congenital microcephaly has been associated with Zika virus infection in Brazil. While there are other causes of microcephaly, there has been a surge in the number of cases during the Zika virus outbreak in that country. Whether or not Zika virus infection is responsible for this birth defect is not known. One report has questioned the surge (1) in microcephaly, suggesting that it is largely attributed to an ‘awareness’ effect.
Current epidemiological data are perhaps insufficient to prove a link of microcephaly with Zika virus infection. However the evidence establishing a causal relationship between Zika and microcephaly is growing as has the body of evidence that demonstrates that Zika could be one of the few pathogens able to cross the placental barrier and infect a foetus.
Given the serious nature of Guillain-Barré and microcephaly, it is prudent for pregnant women to either avoid travel to areas that are endemic for Zika virus infection, or to take measures to reduce exposure to mosquitoes.
There are currently no antiviral drugs or vaccines that can be used to treat or prevent infection with Zika virus. We do have a safe and effective vaccine against another flavivirus, yellow fever virus. Substituting the gene encoding the yellow fever E glycoprotein with that from Zika virus might be a good approach to quickly making a Zika vaccine. However testing of such a vaccine candidate might require several years.
Mosquito control is the only option for restricting Zika virus infection. Measures such as wearing clothes that cover much of the body, sleeping under a bed net, and making sure that breeding sites for mosquitoes (standing water in pots and used tires) are eliminated are examples. Reducing mosquito populations with insecticides may also help to reduce the risk of infection.
Oxitec first unveiled (2) its large-scale, genetically-modified mosquito farm in Brazil in July 2012, with the goal of reducing “the incidence of dengue fever,” as The Disease Daily reported (3). Dengue fever is spread by the same Aedes mosquitoes which spread the Zika virus — and though they “cannot fly more than 400 meters,” WHO stated, “it may inadvertently be transported by humans from one place to another.” By July 2015, shortly after the GM mosquitoes were first released into the wild in Juazeiro, Brazil, Oxitec proudly announced (4) they had “successfully controlled the Aedes aegyptimosquito that spreads dengue fever, chikungunya and zika virus, by reducing the target population by more than 90%.”
It is not surprising that Zika virus has spread extensively throughout the Americas. This area not only harbours mosquito species that can transmit the virus, but there is little population immunity to infection. Infections are likely to continue in these areas, hence it is important to determine whether or not Zika virus infection has serious consequences. Moreover evidence suggests that humans may act as an amplifying host for Zika (unlike Dengue for example) and thus person-mosquito-person transmission may be very common, hence a rapid spread into and throughout urban areas.
Recently, Zika virus was identified in multiple US states, including Texas, New York, and New Jersey, in international travellers returning to the US . Such isolations are likely to continue as long as infections occur elsewhere. Whether or not the virus becomes established in the US is a matter of conjecture. West Nile virus, which is spread by culecine mosquitoes, entered the US in 1999 and rapidly spread across the country. In contrast, Dengue virus, which is spread by Aedes mosquitoes, has not become endemic in the US.
What I have been fascinated by is the tone adopted by different public health and microbiology “camps”. Articles by numerous highly specialised scientists have both urged caution before we conclusively state that “Zika causes microcephaly” and warned us that Zika is the new Ebola only much much worse. Personally, I always thought that good science is evidence-based and a good scientist attempts to educate not frighten and always, ALWAYS adopts a moderate open-minded approach. Based on some of the salaries that contributors to the popular press on both sides of “the pond” enjoy, I’ve clearly been doing it wrong for years.