Prioritizing the ‘Dormant’ Flaviviruses
Prioritizing the 'Dormant' Flaviviruses
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2017 International Association for Ecology and Health
Probably the most disturbing fact of the ongoing Zika
epidemic is that this virus is not new. Zika is not new to
science, as SARS coronavirus was when it first emerged in
2003, nor did it experience dramatic evolutionary change
like influenza does through reassortment. Instead, Zika has
been lurking in the shadows for almost 70 years. It was
hidden in developing countries with poor disease
surveillance, isolated island populations in the Pacific, and poorly
studied animal hosts. We knew about Zika in 1947 when it
was discovered in a jungle in Uganda. We knew the
epidemic potential when Zika barraged through Micronesia in
2007. In retrospect, we should have also been aware of its
link to microcephaly in the Pacific island outbreaks. We
knew the possibility of sexual transmission when an
American mysteriously infected his wife after returning
from a field trip in Senegal in 2008. Yet, we were still
unprepared.
In the past two years, the scientific community has
rallied to combat the Zika outbreak and fill the
longstanding deficit of Zika knowledge. More than 30 candidate
vaccines are in development, and scientific papers on the
virus are more than ten times as abundant as Zika
publications before 2014. Important aspects about the virus’
biology and transmission, like its tissue tropism, interaction
with Dengue, persistence in body fluids, and its structure
have been elucidated. However, this wealth of knowledge
only came after Zika was declared a public health
emergency, opening up research dollars and scientific
opportunity.
Zika virus is one of 53 viruses in the genus flavivirus
currently recognized by the International Committee on
Taxonomy of Viruses. Five of these are big hitters, causing
epidemics and widespread morbidity and mortality: West
Nile virus, Yellow Fever virus, Japanese Encephalitis virus,
Dengue virus, and now Zika virus. Twenty-one other
flaviviruses are known to cause infections in humans. Perhaps
more than any other viral genus, it seems the flaviviruses
are especially primed for human infection: RNA viruses
with high mutation rates, vector-borne, and found in a
wide range of vertebrate and invertebrate hosts.
Unsurprisingly, the flaviviruses that only rarely infect humans, or
have yet to do so, are vastly understudied with research
output for most viruses in this group having plateaued in
the years immediately following their discovery. With the
exception of a big push by the Rockefeller Foundation and
US Government to characterize arboviruses in the 1940s
and 1950s that led to the discovery of many of these viruses,
there has been a paucity of studies investigating these
‘dormant flaviviruses’ over the last 40 years.
Our global approach to emerging infectious disease
research has been reactive for too long, with an increase in
scientific investigations and funding (e.g., for surveillance,
experimental studies, or countermeasures) only coming
after international spread. Gonza´lez-Salazar et al.’s
manuscript in this issue (2017) uses an ecological niche modeling
approach to identify potential, currently unrecognized,
vertebrate hosts for Zika virus in Mexico. This is an
interesting approach to help target zoonotic disease
surveillance in the animals that may serve as most likely
natural reservoirs, and a good start. We need more
analytical tools like this. We know virtually nothing about the
sylvatic cycle, the vectors, the non-human reservoirs, or the
general ecology of Zika. International efforts to map the
potential distribution of Zika are focused on Aedes aegypti
and A. albopictus, but we lack knowledge on the 17 other
mosquito species that have been tested positive over the
years, nor what other viruses these vectors may carry.
We need more predictive tools to forecast the risk that
viruses pose before they become epidemics or pandemics.
We need creative approaches, and multi-disciplinary
collaborations to develop these sets of tools. Mathematical
modelers need to work with field scientists, clinicians,
bioinformaticians, virologists, and veterinarians, and we all
need to collaborate more with laboratory scientists who can
design experiments to validate our models. If phylogenetic
and structural models predict an increase in host range for
a virus, how can we design in vitro or in vivo experiments
to test this? How can we make the most of the scattered
information available on host range, vector range, and viral
biology from the last 70+ years of disjunct studies to better
prioritize the 53 known flaviviruses for future research?
Yaounde virus, Kedougou virus, and Sepik virus are hardly
household names, but they are the closest known relatives
to viruses we know well—West Nile, Zika, Yellow Fever.
How many more flaviviruses will we discover in ecosystems
around the world if we make a concerted effort to find
them? How can we then include these novel viruses into
our prioritizatio (...truncated)