3.3.2. Understanding Filovirus Natural History
UMVE studied the factors implicated in the three steps that led to Ebola virus and Marburg virus diseases emergence in humans. These steps include: the identification of reservoir species, the circulation within the natural host, the crossing to intermediary animal species, and finally the direct transmission to humans from great apes and fruit bats. Antibodies and nucleotide sequences specific for Ebola virus were detected in the liver and spleen of fruit bat belonging to three species (
Hypsignathus monstrosus,
Epomops franqueti,
Myonycteris torquata) in Gabon and Republic of the Congo (
Figure 4). Antibodies and nucleotide sequences specific for Marburg virus were found in the Egyptian fruit bat (
Rousettus aegyptiacus) in Gabon, suggesting that bats might be reservoirs for filoviruses [
3,
4,
5].
Figure 4.
Field Biosafety and Trapping Potential Ebola Virus Reservoir Bats in Gabon.
Figure 4.
Field Biosafety and Trapping Potential Ebola Virus Reservoir Bats in Gabon.
We showed that Ebola virus caused extensive epizootics among gorillas and chimpanzees, killing thousands of animals during the last decade in parts of Gabon and Republic of the Congo [
4]. We characterized the viral variants associated with all Ebola virus disease outbreaks that occurred between 1996 and 2008 and developed new epidemiological models of Ebola virus disease epidemics, based on the identification of several independent epidemic chains. The identification of multiple variants during the 2001 Gabon/Republic of Congo outbreak and two phylogenetically divergent lineages suggest independent introductions into great ape and human populations following multiple viral spillovers from a reservoir host [
6,
7]. In this “multi-emergence” hypothesis, Ebola virus disease outbreaks would occur episodically during certain ecological conditions caused by habitat disturbances or climatic phenomena. This hypothesis also implicitly assumes that Ebola virus was present in Equatorial Africa long before the first documented disease outbreak in 1976, as supported by various serological surveys. Furthermore, we recently showed that the 2007 Luebo outbreak in the Democratic Republic of the Congo was linked to massive fruit bat migration, strongly suggesting that humans could be infected directly by bats or by consumption of bats [
8].
3.3.3. Ebola Virus Disease Pathogenesis
In the study of immunological mechanisms of Ebola virus disease humans, we showed that fatal infection is associated with aberrant innate immunity and global suppression of adaptive immunity [
9,
10,
11,
12]. The innate immune reaction is characterized by a ‘cytokine storm’, with a hyper secretion of numerous pro-inflammatory cytokines, chemokines and growth factors, and by the noteworthy absence of antiviral interferon (IFN)-α [
9,
13,
14]. Immunosuppression of adaptive immunity is characterized by very low levels of circulating cytokines produced by T lymphocytes and by massive loss of peripheral CD4 and CD8 lymphocytes, probably through Fas/FasL-mediated apoptosis. Finally, we hypothesized that a viral protein with super-antigen activity might be involved in the massive T cell apoptosis [
15]. In striking contrast with fatal outcome, effective control of Ebola virus infection is associated with balanced immune responses in survivors. Asymptomatic Ebola virus infection was demonstrated in humans during the 1996-97 disease outbreak in Gabon [
16]. Asymptomatic infection was associated with an early strong inflammatory response that may be involved in the early inhibition of viral replication [
16,
17]. Consistent with this discovery, we showed a decade later that a large fraction of the human population living in forested areas of Gabon has both humoral and cellular immunity to Ebola virus [
18]. In the absence of identified risk factors, the high prevalence of ‘immune’ individuals suggests a common source of human exposure such as fruits contaminated by bat saliva.
Initially focused on Ebola virus disease, UMVE science policy was redirected since 2007 by expanding the main research themes to other emerging viral diseases that could threaten public health in the Congo basin (
Table 1) [
19,
20,
21,
22].
3.3.4. Challenges of Conducting Filovirus Research in Gabon
CIRMF is geographically isolated from the capital of Gabon, Libreville. The Libreville office is essential to the Franceville headquarters as it coordinates visits from staff on field missions, and forwards imported equipment to headquarters. The capital is accessible by a 12-hour ride in a four-wheel drive vehicle or in a train (three times/week schedule) covering 641 km. Due to tropical weather, four weekly domestic plane rotations often fly on an inconsistent schedule. Ultimately CIRMF needs to be largely autonomous in term of electrical power (i.e.,: unexpected fuel supply disruption), cold chain with the necessity to maintain in situ a unit of liquid nitrogen production (repository), and purified water supply.
Table 1.
Viruses identified by the Emerging Viral Unit using CIRMF high containment facilities.
Table 1.
Viruses identified by the Emerging Viral Unit using CIRMF high containment facilities.
Family | Genus/Virus * | Origin/Country ** | Year | Host | Genetics/virus isolates *** |
---|
Filoviridae | Ebolavirus/Ebola virus **** | Mayibout 2/Gabon | 1996 | Human | +/+ |
| Ebolavirus/Ebola virus | Booué/Gabon | 1997 | Human | +/+ |
| Ebolavirus/Ebola virus | Mendemba/Gabon | 2001 | Human | +/+ |
| Ebolavirus/Ebola virus | Makokou/Gabon | 2002 | Human | +/+ |
| Ebolavirus/Ebola virus | Ilahounéné/Gabon | 2002 | Human | +/+ |
| Ebolavirus/Ebola virus | Ekatangaye/Gabon | 2002 | Human | +/+ |
| Ebolavirus/Ebola virus | Ekata/Gabon | 2001 | Human | +/+ |
| Ebolavirus/Ebola virus | Olloba/Gabon | 2001 | Human | +/+ |
| Ebolavirus/Ebola virus | Mbomo/Gabon | 2002 | Human | +/+ |
| Ebolavirus/Ebola virus | Yembelengoye/Gabon | 2003 | Human | +/+ |
| Ebolavirus/Ebola virus | Mvoula/RC * | 2003 | Human | +/+ |
| Ebolavirus/Ebola virus | Mbandza/RC | 2003 | Human | +/+ |
| Ebolavirus/Ebola virus | Etoumbi/RC | 2005 | Human | +/+ |
| Ebolavirus/Ebola virus | Luebo/RDC | 2007 | Human | +/+ |
| Ebolavirus/Ebola virus | Luebo/RDC | 2008 | Human | +/+ |
| Ebolavirus/Ebola virus | Ekata/Gabon | 2002 | Bat | +/- |
| Ebolavirus/Ebola virus | /Gabon | 2002 | Chimp | +/- |
| Ebolavirus/Ebola virus | /Gabon | 2002 | Gorilla | +/- |
| Ebolavirus/Ebola virus | /Gabon | 2002 | Duiker | +/- |
| Ebolavirus/Ebola virus | /Gabon | 2003 | Chimp | +/- |
| Ebolavirus/Ebola virus | /Gabon | 2003 | Gorilla | +/- |
| Ebolavirus/Ebola virus | /RC | 2005 | Chimp | +/- |
| Ebolavirus/Ebola virus | /RC | 2005 | Gorilla | +/- |
| Marburgvirus/Marburg virus | Lambaréné/Gabon | 2005 | Bat | +/- |
| Marburgvirus/Marburg virus | Tchibanga/Gabon | 2006 | Bat | +/- |
| Marburgvirus/Marburg virus | Makokou/Gabon | 2009 | Bat | +/- |
Togaviridae | Alphavirus/Chikungunya virus | Malabo/EG | 2007 | Human | +/- |
| Alphavirus/Chikungunya virus | Libreville/Gabon | 2007–2008 | Human | +/+ |
| Alphavirus/Chikungunya virus | Oyem/Gabon | 2007 | Human | +/+ |
| Alphavirus/Chikungunya virus | Lambaréné/Gabon | 2008–2009 | Human | +/+ |
| Alphavirus/Chikungunya virus | Ndjolé/Gabon | 2008 | Human | +/+ |
| Alphavirus/Chikungunya virus | Lastourville/Gabon | 2007 | Human | +/+ |
| Alphavirus/Chikungunya virus | Franceville/Gabon | 2010 | Human | +/+ |
| Alphavirus/Chikungunya virus | /Gabon | 2007–2010 | Human | +/+ |
| Alphavirus/Chikungunya virus | Brazzaville/RC | 2011 | Human | +/+ |
| Alphavirus/Chikungunya virus | /RDC | 2010–2011 | Human | +/- |
| Alphavirus/Chikungunya virus | /Gabon | 2007–2010 | Mosquito | +/- |
Flaviviridae | Flavivirus/Dengue virus 2 | Libreville/Gabon | 20072008 | Human | +/+ |
| Flavivirus/Dengue virus 2 | Oyem/Gabon | 2007 | Human | +/+ |
| Flavivirus/Dengue virus 2 | Lambaréné/Gabon | 2008–2009 | Human | +/+ |
| Flavivirus/Dengue virus 2 | Ndjolé/Gabon | 2008 | Human | +/+ |
| Flavivirus/Dengue virus 2 | Lastourville/Gabon | 2007 | Human | +/+ |
| Flavivirus/Dengue virus 2 | Franceville/Gabon | 2010 | Human | +/+ |
| Flavivirus/Dengue virus 2 | /RDC | 2011 | Human | +/- |
| Flavivirus/Dengue virus 2 | /Gabon | 2007–2010 | Mosquito | +/- |
| Flavivirus/Dengue virus 1 | Libreville/Gabon | 2007–2008 | Human | +/+ |
| Flavivirus/Dengue virus 1 | Lambaréné/Gabon | 2008–2009 | Human | +/+ |
| Flavivirus/Dengue virus 1 | Franceville/Gabon | 2010 | Human | +/+ |
| Flavivirus/Dengue virus 1 | /RDC | 2011 | Human | +/- |
| Flavivirus/Dengue virus 3 | Franceville/Gabon | 2010 | Human | +/+ |
Flaviviridae | Flavivirus/Zika virus | Libreville/Gabon | 2007 | Human/Mosquito | +/- |
| Flavivirus/Wesselsbron virus | /Gabon | 2010 | Duiker | +/- |
| Flavivirus/Spondweni virus | /Gabon | 2010 | Duiker | +/- |
Bunyaviridae | Nairovirus/CCHFV | /RDC | 2009 | Human | +/- |
| Phlebovirus/RVFV * | /Gabon | 2011 | Tick | +/- |
Picornaviridae | Enterovirus/PV1 | Pointe Noire/RC | 2010 | Human | +/+ |
| Rhinovirus/UT ***** | /Gabon | 2010–2012 | Human | +/- |
| Parechovirus/UT | /Gabon | 2010–2012 | Human | +/- |
| Parechovirus/UT | /Gabon | 2010–2012 | Human | +/- |
| Enterovirus/UT | /Gabon | 2011 | Monkeys | +/- |
Coronaviridae | Coronavirus/HCoV NL63 | /Gabon | 2010–2012 | Human | +/- |
| Coronavirus/HCoV HKU1 | /Gabon | 2010–2012 | Human | +/- |
| Coronavirus/HCoV OC43 | /Gabon | 2010–2012 | Human | +/- |
| Coronavirus/HCoV 229E | /Gabon | 2010–2012 | Human | +/- |
| Coronavirus/UT | /Gabon | 2005–2009 | Bat | +/- |
Paramyxoviridae | Pneumovirus/hRSV | /Gabon | 2010–2012 | Human | +/- |
| Respirovirus/PIV 1 | /Gabon | 2010–2012 | Human | +/- |
| Rubulavirus/PIV 2 | /Gabon | 2010–2012 | Human | +/- |
| Respirovirus/PIV 3 | /Gabon | 2010–2012 | Human | +/- |
| Rubulavirus/PIV 4 | /Gabon | 2010–2012 | Human | +/- |
| Metapneumovirus/hMPV | /Gabon | 2010–2012 | Human | +/- |
| Rubulavirus/UT | /Gabon | 2005–2009 | Bat | +/- |
| Morbillivirus/UT | /Gabon | 2005–2009 | Bat | +/- |
| Henipavirus/UT | /Gabon | 2005–2009 | Bat | +/- |
Orthomyxoviridae | Influenzavirus A/FLUAV H1N1 | /Gabon | 2010–2012 | Human | +/- |
| Influenzavirus A | /Gabon | 2010–2012 | Human | +/- |
| Influenzavirus B | /Gabon | 2010–2012 | Human | +/- |
Adenoviridae | Adenovirus/UT | /Gabon | 2010–2012 | Human | +/- |
Reoviridae | Rotavirus/UT | /Gabon | 2010–2012 | Human | +/- |
Caliciviridae | Sapovirus/UT | /Gabon | 2010–2012 | Human | +/- |
| Norovirus/NoVG2/2 | /Gabon | 2010–2012 | Human | +/- |
| Norovirus/NoV1/2 | /Gabon | 2010–2012 | Human | +/- |
Astroviridae | Astrovirus/Human astrovirus | /Gabon | 2010–2012 | Human | +/- |
Herpesviridae | Simplexvirus/HSV1 & HSV2 | /Gabon | 2010–2012 | Human | +/- |
| Simplexvirus/HSV1 & HSV2 | /Gabon | 2010–2011 | Human | +/- |
| Varicellovirus/VZV | /Gabon | 2010–2012 | Human | +/- |
| Varicellovirus/VZV | /Gabon | 2010–2011 | Human | +/- |
| Cytomegalovirus/CMV | /Gabon | 2010–2012 | Human | +/- |
| Cytomegalovirus/CMV | /Gabon | 2010–2011 | Human | +/- |
| Roseolovirus/HHV6 | /Gabon | 2010–2012 | Human | +/- |