In 2005, a strain of the Chikungunya virus that arose in east Africa spread to the islands of Comoros, Mayotte, Seychelles and Reunion in the south-western Indian Ocean.

Later that year, the virus began to cause large-scale outbreaks in India. The following year, some 1.4 million people in various parts of this country fell victim to the virus.

Since 2007, this virus belonging to the East, Central and South African (ECSA) lineage has been spreading in South-East Asian countries, replacing a virus of Asian lineage that had been circulating there for the past 60 years.

Chikungunya is primarily spread by the Aedes aegypti mosquito that breeds in household water containers. However, during the outbreaks on Reunion Island, it was found that the virus had been become adapted for efficient transmission by Aedes albopictus, the Asian tiger mosquito that originated in South-East Asia and is now found in many countries across the globe.

The route

When the mosquito feeds on an infected person, it draws in the virus along with its blood meal. In order to infect people that the mosquito bites subsequently, the virus must make its way from the insect's digestive tract and get to the salivary glands.

The ability of the virus to easily spread via the Ae. albopictus mosquito has been attributed to one particular mutation in its E1 glycoprotein. This molecule gives the virus entry to cells lining the insect's gut.

Alanine to valine

In separate papers published in 2007, scientists at the Institut Pasteur in France and the University of Texas Medical Branch at Galveston in the U.S. drew attention to the change in amino acid, from alanine to valine, at position 226 in the E1 glycoprotein.

A switch of just one ‘letter' in the genetic sequence that coded for the protein was all that it took to bring about this change.

But in further research that is being published this week in the Proceedings of the National Academy of Sciences of the U.S.A. (PNAS), scientists at the University of Texas Medical Branch in Galveston have taken a closer look at the adaptation to Ae. albopictus.

Although Ae. albopictus is native to South-East Asia, there was no evidence that this species had played a major role in transmission in that region of the Chikungunya virus of the Asian lineage, pointed out Konstantin Tsetsarkin and others in the paper.

However, the mosquito has been implicated in the recent epidemics involving the introduced ECSA strain.

If a single mutation was all that was required, why did it not happen in the Asian lineage of the virus that had been circulating for several decades in South-East Asia where Ae. albopictus is ubiquitous?

Complementary

In their paper, the scientists point to another complementary modification in the E1 glycoprotein that was necessary for the change of amino acid at position 226 to take effect. The amino acid at position 78 needed to be alanine, not threonine.

When a virus of the Asian lineage was engineered in the laboratory with valine at position 226 in its E1 glycoprotein, its infectivity for Ae. albopictus was not significantly different from a similar virus with alanine in that position.

When, however, the virus was engineered with alanine at position 78 as well as valine at position 226, its infectivity in the mosquito shot up nearly a 100-fold.

The experiments

Experiments carried out by the scientists also showed that these adaptive changes in the E1 glycoprotein did not compromise viral fitness for transmission by Ae. aegypti.

The virus of east African origin already possessed alanine at position 78 and therefore just one further mutation, at position 226, sufficed to adapt it for efficient transmission through Ae. albopictus. The virus of Asian lineage, on the other hand, needed two mutations to achieve the same goal.

The explanation

“The need for two mutations appears to explain why the virus did not adapt to Ae. albopictus in South-East Asia, and why the strain that spread there from India a few years ago is now displacing the older South-East Asian lineage,” remarked Scott Weaver, who holds the John Sealy Distinguished University Chair in Human Infections and Immunity and is senior author of the paper, in an email.

Recent outbreaks

The recent South-East Asian outbreaks caused by the ECSA strain appeared to be larger and affected regions where Ae. albopictus was more abundant than Ae. aegypti. Some regions, like Bangkok, where the former was less common had been spared.

Minor genetic differences among viral lineages can have dramatic and unanticipated effects on their ability to emerge and cause human disease, he pointed out.

Had the old Asian lineage been able to adapt to Ae. albopictus via a single mutation, South-East Asia would probably have had much larger epidemics during the past 60 years.

The same thing could have happened in India too from the 1950s to the 1970s when the virus of Asian lineage was circulating.

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