International Society for Infectious Diseases

Date: Sat 20 Oct 2007
Source: SciDevNet [edited]

Ebola viruses ‘capable of merging’ into new strains
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Scientists have discovered that a strain of Ebola virus isolated from
wild apes in the Gabon/Congo region belongs to a new lineage and is
capable of genetically merging with other strains of the virus to
create new variants.

This ability of the lethal virus to ‘recombine’ genetic material has
important implications for vaccine development, write the
researchers. A vaccine that is made up of weakened viruses could
merge with the wild virus to form new strains, making the spread of
the virus in humans and apes harder to predict and control. The
findings were published online this week (17 Oct 2007) in the
Proceedings of the National Academy of Sciences [Reference:
Proceedings of the National Academy of Sciences doi 10.1073/pnas.
0704076104 (2007)/
www.pnas.org

Scientists from the International Centre for Medical Research in
Franceville, Gabon, and their colleagues genetically analysed samples
of Zaire Ebola virus -- the most virulent type, which causes
haemorrhagic fever and death within days in almost 90 percent of
infected people -- taken from carcasses of great apes. They
identified a new strain, strain B, that is genetically different from
the strain A samples collected in past outbreaks from infected
humans. The researchers estimate that strain B probably evolved just
before the 1st recorded human outbreak in 1976. They confirmed that
it was the cause of outbreaks in humans in the Republic of Congo in
2003 and 2005.

This discovery indicates that outbreaks in humans could be caused not
just by strain A, which is spreading through central Africa, but also
by multiple emerging viruses. There is evidence that the A and B
strains may have recently recombined to form a group of recombinant
viruses that triggered outbreaks in 2001-03.

The researchers hope that their findings will help to develop better
methods for predicting and controlling outbreaks. But we still need
to know more about how human outbreaks occur, study author Jean-Paul
Gonzales, from the Research Institute for Development at Mahidol
University in Thailand, told SciDev.Net. For example, we need to know
whether recombinant strains are the main source of infection and more
about the role of bats as a viral reservoir.

[Byline: Esther Tola]

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Ebola haemorrhagic fever emerged in Central Africa in 1976, and 3
African subtypes of Ebola virus are now recognised: Sudan ebolavirus
and Zaire ebolavirus were isolated in 1976 and Cote d’Ivoire
ebolavirus in 1994. (A 4th subtype — Reston ebolavirus — not so far
associated with serious human disease, was isolated in a colony of
monkeys imported into the USA from the Philippines in 1989). Zaire
ebolavirus is the subtype responsible for the current outbreak of
haemorragic fever in the Democratic Republic of the Congo (see DR
Congo references below).

Among the various animals suspected of involvement in the the
transmission of Ebola fever, 3 species of fruit bats (suborder
_Megachiroptera_) have been found to be asymptomatically infected
with Ebola virus: _Hypsignathus monstrosus_ (hammer-headed fruit
beats), _Epomops franqueti_ (singing fruit bats), and _Myonycteris
torquata_ (little collared fruit bats). But it is not known whether
these species are incidental hosts or a reservoir of ebolavirus
infection for humans and other terrestrial mammals. Great apes are
particularly sensitive to lethal Ebola virus infection and bat-saliva
contaminated fruit may be one route of exposure of terrestrial
mammals to Ebola virus. Such a chain of events may occur sporadically
at different sites depending on specific environmental factors (see:
Curr Top Microbiol Immunol. 2007;315:363-87). The PNAS paper by
Tatiana J. Wittmann and colleagues, on which the preceding new
article is based, concerns further genetic characterisation of Ebola
virus by the genome sequencing of isolates of Zaire ebolavirus from
wild apes. This reveals both a new genetic lineage and evidence of
recombination (“Isolates of Zaire ebolavirus from wild apes reveal
genetic lineage and recombinants,” PNAS doi10.1073/pnas.0704076104
(2007)
<http://www.pnas.org/cgi/content/abstract/0704076104v1>.

Tatiana J. Wittmann, et al., state that: “Over the last 30 years,
Zaire ebolavirus, a virus highly pathogenic for humans and wild apes,
has emerged repeatedly in Central Africa. Thus far, only a few virus
isolates have been characterized genetically, all belonging to a
single genetic lineage and originating exclusively from infected
human patients. Here, we describe the 1st Zaire ebolavirus sequences
isolated from great ape carcasses in the Gabon/Congo region that
belong to a previously unrecognized genetic lineage. According to our
estimates, this lineage, which we also encountered in the 2 most
recent human outbreaks in the Republic of the Congo in 2003 and 2005,
diverged from the previously known viruses around the time of the 1st
documented human outbreak in 1976. These results suggest that virus
spillover from the reservoir has occurred more than once, as
predicted by the multiple emergence hypothesis. However, the young
age of both Zaire ebolavirus lineages and the spatial and temporal
sequence of outbreaks remain at odds with the idea that the virus
simply emerged from a long-established and widespread reservoir
population. Based on data from 2 Zaire ebolavirus genes, we also
demonstrate, within the family _Filoviridae_, recombination between
the 2 lineages. According to our estimates, this event took place
between 1996 and 2001 and gave rise to a group of recombinant viruses
that were responsible for a series of outbreaks in 2001-2003. The
potential for recombination adds an additional level of complexity to
unraveling and potentially controlling the emergence of ZEBOV in
humans and wildlife species.”

These findings are novel and significant in 2 respects. They reveal
heterogeneity among isolates of Zaire ebolavirus possibly indicating
multiple routes of transmission to terrestrial mammals and the
existence of distinct lineages. It will be of interest to establish
the lineage relationship of the virus responsible for the current
outbreak in the DR Congo. In addition Wittmann, et al., appear to
have obtained evidence of variation arising by genetic recombination,
a surprising finding in view of the rarity of recombination in
viruses with single-stranded negative-sense RNA genomes. – Mod.CP]