ONEAccording to the World Health Organization, the Zika virus was first isolated from an infected monkey in Uganda in 1947. Since then there have been only sporadic cases on the African continent. In contrast, thousands of people in America and Asia have been infected in multiple outbreaks since 2007. At its worst, the virus spread to more than 60 countries in 2016 and was involved in around 5,000 cases of microcephaly – a serious birth defect that a baby’s head is much smaller than expected.
The authors of a study published today (November 19) in Science offers a possible explanation for the havoc Zika wreaked outside of African countries. They show that the subspecies of the mosquito vector Aedes aegypti, which lives in close proximity to humans in the tropical urban areas of Asia and America, is more likely to both contract and transmit the Zika virus than the subspecies more common in Africa.
“It is the first really convincing evidence that these populations differ in susceptibility to viruses that cause human disease,” said Jeffrey Powell, a mosquito geneticist at Yale University who was not involved in the study.
Aedes aegypti formosus (Aaf) lives in both forests and urban areas in sub-Saharan Africa and ingests blood meals from various vertebrates, including humans. Aedes aegypti aegypti (Aaa), believed to be a common ancestor, bites and prefers to live next to people – often in urban settings where women lay eggs in containers such as buckets and old tires. Comparisons have shown that the two subspecies can be differentiated and crossed based on their genome.
Aaa is present in some African coastal countries, but invaded other parts of the world from the 16th century when international trade was flourishing. Nowadays, the subspecies lives on every continent except Antarctica and is the main vector for the viruses that cause dengue, yellow fever, and zika, which can cause rashes, muscle pain, mild fever and, in severe cases, microcephaly and other problems to develop in fetuses.
Louis Lambrechts, who studies mosquitoes and their interactions with viruses at the Pasteur Institute in Paris, and his team began to focus on the Zika virus a few years ago. They were interested in why the Zika virus is not an equal problem all over the world and whether or not the development of the aaa mosquito is affecting the ability to transmit viruses. While it is clear that this subspecies adapted to life with humans, it is not known whether “this adaptation to the home environment was accompanied by a change in their intrinsic ability to acquire the virus”.
The researchers fed each of the eight groups of mosquitoes, originally from blood meals in Africa, America and Asia, and spiked with one of six strains of the Zika virus. They found that the mosquitoes collected from America and Asia required a lower virus titer to become infected than the insects from Africa. The susceptibility of eight mosquito populations collected from all over Africa to two Zika virus strains was then measured. The insects from the Senegalese coastal area, where the subspecies Aaa and Aaf likely mix, required the lowest virus dose in an artificial blood meal to become infected.
The authors also showed that the Aaa subspecies was more prone to Zika infection than the African subspecies after feeding an infected animal – in this case a mouse. Aaa mosquitoes were more likely than their counterparts to have live viruses in their saliva after infection, which means that Aaa is not only more susceptible to viral infection, but also tends to transmit the Zika virus afterwards when they feed on a person.
Finally, Lambrechts and colleagues crossed African and non-African mosquitoes and showed that one or more genes on the second mosquito chromosome likely contributed to the difference in Zika sensitivity between the two strains.
The authors provide a robust link between the mosquito and mosquito domestication process. . . What this made possible with regard to the emergence and subsequent spread of the Zika virus across America, ”says Moritz Kraemer, an infectious disease researcher at Oxford University who was not involved in the work. “You answer some of these questions about why the transmission in America and parts of Asia is much higher than in many parts of Africa.”
“There may be other explanations,” says Lambrechts, but the differences in susceptibility between these two subspecies can help prevent major outbreaks in Africa.
Another way to consider the mutually exclusive hypothesis, Powell said, is that genetic modifications to the virus allowed it to specialize in mosquito populations outside of Africa and become more infectious. “These viruses are RNA-based viruses. They have very high mutation rates and very short generation times so they can adapt very quickly, ”he adds. “Between the mosquito and the virus, the virus has the advantage that it can develop much faster.”
The authors considered the possible influence of viral genetic variation considering a group of seven Zika virus strains, says Lambrechts. “The African mosquitoes were less susceptible to Zika virus infections than the non-African ones, regardless of the virus strain. Our conclusions about the different susceptibility of the Zika virus to the subspecies Aedes aegypti therefore go beyond the genetic diversity of the viruses. “
However, he admits that both mosquito and virus diversity could make a contribution. His group recently showed in a preprint that there are natural differences in the transferability and pathogenicity between Zika virus strains from different locations.
F. Aubry et al., “Improved Zika Virus Susceptibility to Globally Invasive Aedes aegypti Populations”. science, doi: 10.1126 / science.abd3663, 2020.