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In the middle of the last decade two little known, and previously geographically restricted mosquito-borne viruses - Chikungunya and Zika – both broke out of Africa and began to travel across the Indian Ocean, into Asia, the South Pacific, and eventually the Americas.
Of the two, Chikungunya has spread the farthest, and the fastest, infecting well over 1.5 people in the Americas in the past two years (see CDC Updated Travel Notices: Chikungunya In Mexico & Central America).
CHKV’s rapid rise has been linked to mutation in the envelope protein gene (E1-A226V) of the virus that allowed the Aedes Albopictus or `Asian tiger’ mosquito to transmit the virus more efficiently (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential). This genetic change appears to have occurred roughly a decade ago.
While originally described as being a painful, but self-limiting and rarely fatal infection, we are seeing increasing evidence that CHKV can produce serious, even life threatening illness in a small subset of its victims (see Chikungunya virus–associated encephalitis: A cohort study on La Réunion Island, 2005–2009 by Patrick Gérardin, MD, PhD et al. & Eurosurveillance Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015).
Despite their similar histories, until the past few months, Zika has taken a backseat to the more aggressively spreading Chikungunya virus. It arrived in the the South Pacific in 2007, but languished there, at least until a year or so ago when it helped spark an epidemic in French Polynesia late last year.
Suddenly Zika has begun spreading rapidly in South & Central America, and we are seeing what appears to be new (or at least, previously unreported) complications of infection; birth defects due to maternal infection and a rise in Guillain–Barré syndrome (GBS) (see ECDC: Complications Potentially Linked To The Zika Virus Outbreaks In Brazil & French Polynesia).
Perhaps explaining this sudden surge and increased virulence, researchers at the University of Sao Paulo and the Pasteur Institute of Dakar (Senegal) have uncovered genetic changes in the Zika virus that occurred after the virus reached the South Pacific in 2007, that appear to make it better adapted to human physiology.
The paper has not yet been published in a peer-reviewed journal, but has been offered as a preview on the BioRxiv (Bio Archive) site while awaiting publication.
That said, the authors are published researchers attached to major institutions, and this work builds on a previously published paper (see Molecular evolution of Zika virus, an neglected emerging disease in Africa and Asia) by several of these same researchers.
Spread of the pandemic Zika virus lineage is associated with NS1 codon usage adaptation in humans
Caio Cesar de Melo Freire, Atila Iamarino, Daniel Ferreira de Lima Neto, Amadou Alpha Sall, Paolo Marinho de Andrade Zanotto
doi: http://dx.doi.org/10.1101/032839
Abstract
Zika virus (ZIKV) infections were more common in the zoonotic cycle until the end of the 20th century with few human cases in Africa and Southeastern Asia. Recently, the Asian lineage of ZIKV is spreading along human-to-human chains of transmission in the Pacific Islands and in South America. To better understand its recent urban expansion, we compared genetic differences among the lineages.
Herein we show that the recent Asian lineage spread is associated with significant NS1 codon usage adaptation to human housekeeping genes, which could facilitate viral replication and increase viral titers.
These findings were supported by a significant correlation with growth in Malthusian fitness. Furthermore, we predicted several epitopes in the NS1 protein that are shared between ZIKV and Dengue. Our results imply in a significant dependence of the recent human ZIKV spread on NS1 translational selection.
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By examining viral samples taken before the middle of the last decade, researchers have identified changes that occurred in 2007 that appear to enhance replication of the virus in humans. This could increase one’s viral load (viremia), and conceivably produce more severe disease.
Higher viral titers would could also facilitate transmission from human – to mosquito – to human, which could help explain the sudden surge in cases.
The full paper is available for inspection. From the Discussion section, the authors write:
The differences between the African and Asian lineages could explain the emergence of ZIKV in humans and raises concerns about the consequences of the adaptive genetic changes observed in NS1 (Figure 1B) and the recent increase in viral fitness (Figure 1C) (Pepin et al., 2010; Longdon et al., 2014).Moreover, the limited number of human ZIKV cases in Africa could be associated to low viremia in humans, which was demonstrated by a health-officer volunteer experimentally infected with a virus from the African lineage that failed to infect A. aegypti mosquitoes (Bearcroft, 1956).
Together, our results suggest that fitness gain is associated with improvement of the NS1 translation in humans by synonymous mutations. Synonymous mutations are a common source of variation, given the constrained nonsynonymous substitutions rate imposed to RNA viruses that have to negotiate successful infections, alternating between humans and mosquitoes (Hanada et al., 2004).
It remains to be evaluated how the NS1 structural and immunological similarities associate to the aggravated symptoms observed when ZIKV and DENV co-circulate (Roth et al., 2014). For this reason, our findings may also be of considerable relevance for the ongoing development of DENV vaccines
