Tuesday, May 16, 2017

Fiocruz Institute: Sequencing Of Yellow Fever Virus Shows 8 Genetic Changes - Brazil


This year's Yellow Fever epidemic in Brazil is the worst in years, and the virus is turning up in urban areas that have not experienced outbreaks in decades (see Brazil: Yellow Fever Updates From The MOH, The CDC, and University of Wisconsin). Complicating matters, there is serious shortage of the Yellow Fever Vaccine (see CDC Announcement: Yellow Fever Vaccine Access).
The reasons behind this sudden surge, and geographic expansion of the virus, have not been established, but a report published yesterday in Memórias do Instituto Oswaldo Cruz may offer a clue.

Researchers sequenced the genome of two recent Yellow Fever viruses isolated from Howler Monkeys - and found a number of novel mutations - amino acid changes that have never been seen in the Yellow Fever virus previously.

First the abstract of the study, followed by some media reports, and then I'll return with an epilogue.


Myrna C. Bonaldo1,+, Mariela Martínez Gómez1, Alexandre A. C. dos Santos1, Filipe Vieira Santos de Abreu2,3, Anielly Ferreira-de-Brito2, Rafaella Moraes de Miranda2, Marcia Gonçalves de Castro2, Ricardo Lourenço-de-Oliveira2


The current yellow fever (YF) outbreak in Brazil is the most severe recently reported in the country. It has rapidly spread to areas where YF viral activity have not been observed for more than seventy years and vaccine coverage is almost null. 

Here, we sequenced the whole YF genome of two naturally infected howler-monkeys (Alouatta clamitans) from the Municipality of Domingos Martins, State of Espírito Santo, Brazil. The ongoing-outbreak genome sequences are identical. They clustered in 1E sub-clade (South America I genotype) together with recent Brazilian and Venezuelan strains characterized from infections in humans and non-humans primates.
However, we detected eight unique amino acid changes in the viral proteins, which are located in the structural capsid protein (1 change), and the components of viral replicase complex, the NS3 (2 changes) and NS5 (5 changes) proteins, suggesting a potential role in the capacity of viral infection to vertebrate and/or invertebrate hosts and spreading in the ongoing outbreak.

One of many media reports on this study can be found in Brazil's Jornal Nacional.

Fiocruz discovers that yellow fever virus in Brazil has mutated
Scientists want to know if mutations influence the spread of disease.
Increased proliferation of the virus rate in the last six months.

Scientists at the Oswaldo Cruz Foundation in Rio, found that the yellow fever virus circulating in Brazil mutated.

The return of yellow fever triggered the alert signal. The rate of contamination was faster: the past six months, 756 cases. Some affected areas did not record the disease for more than seven decades.

Scientists at Fiocruz were to investigate the causes of these phenomena taken from infected mosquito samples and dead monkeys from the disease in the Holy Spirit and in Rio de Janeiro . They found novel mutations in a large part of the genetic code: the one that controls the spread of the virus.
         (Continue . . . )

Whether these specific changes are behind the sudden incrase in Yellow Fever in Brazil remains to be determined, but it was only 12 years ago when we saw a similar event take place with the Chikungunya virus.
During the last half of the 20th century Chikungunya was a little noticed arbovirus - endemic to parts of Central and Eastern Africa - where it caused limited, sporadic outbreaks.

All of that changed in 2005 when the virus abruptly jumped to Reunion Island in the Indian Ocean, where it reportedly infected about 1/3rd of that island’s population (266,000 case out of  pop.770,000) in a matter of a few months. 

From there, aided and abetted by a new mutation that allowed it to be carried by the Aedes Albopictus `Asian tiger’ mosquito (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential), the virus quickly cut a swath across the Indian ocean and into the Pacific.

While vector borne viruses don't tend to mutate as quickly as influenza viruses, they can, and do change over time.  Most of the time those changes have little or no impact on how the virus behaves.  Many render the virus less `biological fit', and quickly fade into evolutionary obscurity. 
But every once in awhile, as we saw with Chikungunya in 2005 - a genetic change can have a big - even global - impact. 
The jury is still out on what has caused Brazil's recent surge and spread in Yellow Fever cases. But at least scientists now have a plausible mechanism to investigate.

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