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The hepatitis C virus genotype 2 (HCV2) is endemic in Western and Central Africa. The HCV2 evolutionary origins remain uncertain due to the paucity of available genomes from African settings. In this study, we investigated the molecular epidemiology of HCV infections in rural Guinea, Western Africa, during 2004 and 2014. Broadly reactive nested reverse transcription polymerase chain reaction (RT-PCR)-based screening of sera from 1,571 asymptomatic adults resulted in the detection of 25 (1.5 per cent; 95 per cent confidence interval 0.9–2.3) positive samples, with a median viral load of 2.54E + 05 IU/ml (interquartile range 6.72E + 05). HCV-infected persons had a median age of 47 years, and 62.5 per cent were male and 37.5 per cent were female. The full polyprotein-encoding genes were retrieved by a combination of high throughput and Sanger sequencing from 17 samples showing sufficiently high viral loads. Phylogenetic analysis and sequence distances ≥13 per cent averaged over the polyprotein genes compared to other HCV2 subtypes revealed nine previously unknown HCV2 subtypes. The time to the most recent common ancestor of the Guinean HCV2 strains inferred in a Bayesian framework was 493 years (95 per cent Highest posterior density (HPD) 453–532). Most of the Guinean strains clustered poorly by location on both the level of sampling sites within Guinea and the level of countries in the phylogenetic reconstructions. Ancestral state reconstruction provided decisive support (Bayes factor > 100) for an origin of HCV2 in Western Africa. Phylogeographic reconstructions in a Bayesian framework pointed to a radial diffusion of HCV2 from Western African regions encompassing today's countries like Ghana, Guinea Bissau, or Burkina Faso, to Central and Northern African regions that took place from the 16th century onwards. The spread of HCV2 coincided in time and space with the main historic slave trade and commerce routes, supported by Bayesian tip-association significance testing (P   = 0.01). Our study confirms the evolutionary origins of HCV2 in Western Africa and provides a potential link between historic human movements and HCV2 dispersion. [ABSTRACT FROM AUTHOR]

Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/HCV interplay upon coinfection. [ABSTRACT FROM AUTHOR]

Active surveillance in health care centers in Gabon during 2009-2011 detected 72 clinical cases of pandemic (H1N1) 2009 (pH1N1). We found that pH1N1 virus was introduced in mid-2009 but spread throughout the country in 2010. Thus, Gabon was also affected by pH1N1. [ABSTRACT FROM AUTHOR]

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne disease well recognized through Europe and Asia where diagnostic tests and medical surveillance are available. However, it is largely neglected in Africa, especially in the tropical rainforest of Central Africa where only sporadic human cases have been reported and date back to more than 30 years. We describe here an isolated human case that occurred in the Democratic Republic of the Congo in 2008 and performed phylogenetic analysis to investigate whether it resulted from a regional re-emergence or from the introduction of a novel virus in the area. Methods and Findings: Near complete segment S and partial segment M sequences were characterized. Bayesian phylogenetic analysis and datation were performed to investigate the relationship between this new strain and viral strains from Africa, Europe and Asia. The new strain is phylogenetically close to the previously described regional genotype (II) that appears to be specific to Central Africa. Phylogenetic discrepancy between segment S and M suggested genetic exchange among local sublineages, which was dated back to 130–590 years before present. Conclusions: The phylogenetic analyses presented here suggest ongoing CCHF virus circulation in Central Africa for a long time despite the absence of reported human cases. Many infections have most probably been overlooked, due to the weakness of healthcare structures and the absence of available diagnostic procedure. However, despite the lack of accurate ecological data, the sporadic reporting of human cases could also be partly associated with a specific sylvatic cycle in Central Africa where deforestation may raise the risks of re-emergence. For these reasons, together with the high risk of nosocomial transmission, public health authorities' attention should be drawn to this etiological agent. Author Summary: Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans through tick-bite or contact with infected blood or tissues from livestock, the main vertebrate hosts in a peri-domestic natural cycle. With numerous outbreaks, a high case fatality rate (3%–30%) and a high risk for nosocomial transmission, CCHFV became a public health concern in Europe and Asia. However virus surveillance in Africa is difficult due to the limited sanitary facilities. Especially, CCHFV occurrence in Central Africa is very poorly described and seems highly in contrast with the temperate to dry environments to which the virus is usually associated with. We described a single human infection that occurred in Democratic Republic of the Congo after nearly 50 years of absence. The phylogenetic analysis suggests that CCHFV enzootic circulation in the area is still ongoing despite the absence of notification, and thus reinforces the need for the medical workers and authorities to be aware of the outbreak risk. The source of infection seemed associated with a forest environment while no link with the usual agro-pastoral risk factors could be identified. More accurate ecological data about CCHFV enzootic cycle are required to assess the risk of emergence in developing countries subjected to deforestation. [ABSTRACT FROM AUTHOR]

Background: Henipaviruses (Hendra and Nipah virus) are highly pathogenic members of the family Paramyxoviridae. Fruiteating bats of the Pteropus genus have been suggested as their natural reservoir. Human Henipavirus infections have been reported in a region extending from Australia via Malaysia into Bangladesh, compatible with the geographic range of Pteropus. These bats do not occur in continental Africa, but a whole range of other fruit bats is encountered. One of the most abundant is Eidolon helvum, the African Straw-coloured fruit bat. Methodology/Principal Findings: Feces from E. helvum roosting in an urban setting in Kumasi/Ghana were tested for Henipavirus RNA. Sequences of three novel viruses in phylogenetic relationship to known Henipaviruses were detected. Virus RNA concentrations in feces were low. Conclusions/Significance: The finding of novel putative Henipaviruses outside Australia and Asia contributes a significant extension of the region of potential endemicity of one of the most pathogenic virus genera known in humans. [ABSTRACT FROM AUTHOR]

Decades after its discovery in East Africa, Zika virus (ZIKV) emerged in Brazil in 2013 and infected millions of people during intense urban transmission. Whether vertebrates other than humans are involved in ZIKV transmission cycles remained unclear. Here, we investigate the role of different animals as ZIKV reservoirs by testing 1723 sera of pets, peri-domestic animals and African non-human primates (NHP) sampled during 2013-2018 in Brazil and 2006-2016 in Côte d'Ivoire. Exhaustive neutralization testing substantiated co-circulation of multiple flaviviruses and failed to confirm ZIKV infection in pets or peri-domestic animals in Côte d'Ivoire ( n =259) and Brazil ( n =1416). In contrast, ZIKV seroprevalence was 22.2% (2/9, 95% CI, 2.8-60.1) in West African chimpanzees ( Pan troglodytes verus ) and 11.1% (1/9, 95% CI, 0.3-48.3) in king colobus ( Colobus polycomos ). Our results indicate that while NHP may represent ZIKV reservoirs in Africa, pets or peri-domestic animals likely do not play a role in ZIKV transmission cycles.

The rising incidence of emerging infectious diseases (EID) is mostly linked to biodiversity loss, changes in habitat use and increasing habitat fragmentation. Bats are linked to a growing number of EID but few studies have explored the factors of viral richness in bats. These may have implications for role of bats as potential reservoirs. We investigated the determinants of viral richness in 15 species of African bats (8 Pteropodidae and 7 microchiroptera) in Central and West Africa for which we provide new information on virus infection and bat phylogeny. We performed the first comparative analysis testing the correlation of the fragmented geographical distribution (defined as the perimeter to area ratio) with viral richness in bats. Because of their potential effect, sampling effort, host body weight, ecological and behavioural traits such as roosting behaviour, migration and geographical range, were included into the analysis as variables. The results showed that the geographical distribution size, shape and host body weight have significant effects on viral richness in bats. Viral richness was higher in large-bodied bats which had larger and more fragmented distribution areas. Accumulation of viruses may be related to the historical expansion and contraction of bat species distribution range, with potentially strong effects of distribution edges on virus transmission. Two potential explanations may explain these results. A positive distribution edge effect on the abundance or distribution of some bat species could have facilitated host switches. Alternatively, parasitism could play a direct role in shaping the distribution range of hosts through host local extinction by virulent parasites. This study highlights the importance of considering the fragmentation of bat species geographical distribution in order to understand their role in the circulation of viruses in Africa.

In recent years, novel henipavirus-related sequences have been identified in bats in Africa. To evaluate the potential of African bat henipaviruses to spread in non-bat mammalian cells, we compared the biological functions of the surface glycoproteins G and F of the prototype African henipavirus GH-M74a with those of the glycoproteins of Nipah virus (NiV), a well-characterized pathogenic member of the henipavirus genus. Glycoproteins are central determinants for virus tropism, as efficient binding of henipavirus G proteins to cellular ephrin receptors and functional expression of fusion-competent F proteins are indispensable prerequisites for virus entry and cell-to-cell spread. In this study, we analysed the ability of the GH-M74a G and F proteins to cause cell-to-cell fusion in mammalian cell types readily permissive to NiV or Hendra virus infections. Except for limited syncytium formation in a bat cell line derived from Hypsignathus monstrosus, HypNi/1.1 cells, we did not observe any fusion. The highly restricted fusion activity was predominantly due to the F protein. Whilst GH-M74a G protein was found to interact with the main henipavirus receptor ephrin-B2 and induced syncytia upon co-expression with heterotypic NiV F protein, GH-M74a F protein did not cause evident fusion in the presence of heterotypic NiV G protein. Pulse-chase and surface biotinylation analyses revealed delayed F cleavage kinetics with a reduced expression of cleaved and fusion-active GH-M74a F protein on the cell surface. Thus, the F protein of GH-M74a showed a functional defect that is most likely caused by impaired trafficking leading to less efficient proteolytic activation and surface expression.

In 2002/2003, a novel coronavirus (CoV) caused a pandemic, infecting more than 8000 people, of whom nearly 10% died. This virus, termed severe acute respiratory syndrome-CoV was linked to a zoonotic origin from rhinolophid bats in 2005. Since then, numerous studies have described novel bat CoVs, including close relatives of the newly emerging Middle East respiratory syndrome (MERS)-CoV. In this paper we discuss CoV genomic properties and compare different taxonomic approaches in light of the technical difficulties of obtaining full genomic sequences directly from bat specimens. We first present an overview of the available studies on bat CoVs, with details on their chiropteran hosts, then comparatively analyze the increase in bat CoV studies and novel genomic sequences obtained since the SARS pandemic. We then conduct a comprehensive phylogenetic analysis of the genera Alpha- and Betacoronavirus, to show that bats harbour more CoV diversity than other mammalian hosts and are widely represented in most, but not all parts of the tree of mammalian CoVs. We next discuss preliminary evidence for phylogenetic co-segregation of CoVs and bat hosts encompassing the Betacoronavirus clades b and d, with an emphasis on the sampling bias that exists among bat species and other mammals, then present examples of CoVs infecting different hosts on the one hand and viruses apparently confined to host genera on the other. We also demonstrate a geographic bias within available studies on bat CoVs, and identify a critical lack of information from biodiversity hotspots in Africa, Asia and Latin America. We then present evidence for a zoonotic origin of four of the six known human CoVs (HCoV), three of which likely involved bats, namely SARS-CoV, MERS-CoV and HCoV-229E; compare the available data on CoV pathogenesis in bats to that in other mammalian hosts; and discuss hypotheses on the putative insect origins of CoV ancestors. Finally, we suggest caution with conclusions on the zoonotic potential of bat viruses, based only on genomic sequence data, and emphasize the need to preserve these ecologically highly relevant animals. This paper forms part of a symposium in Antiviral Research on "from SARS to MERS: 10years of research on highly pathogenic human coronaviruses"., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Serological screening and detection of genomic RNA indicates that members of the genus Henipavirus are present not only in Southeast Asia but also in African fruit bats. We demonstrate that the surface glycoproteins F and G of an African henipavirus (M74) induce syncytium formation in a kidney cell line derived from an African fruit bat, Hypsignathus monstrosus. Despite a less broad cell tropism, the M74 glycoproteins show functional similarities to glycoproteins of Nipah virus.

Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis in tropical and temperate climates. Tropical genotypes 1 and 2 are associated with food-borne and waterborne transmission. Zoonotic reservoirs (mainly pigs, wild boar, and deer) are considered for genotypes 3 and 4, which exist in temperate climates. In view of the association of several zoonotic viruses with bats, we analyzed 3,869 bat specimens from 85 different species and from five continents for hepevirus RNA. HEVs were detected in African, Central American, and European bats, forming a novel phylogenetic clade in the family Hepeviridae. Bat hepeviruses were highly diversified and comparable to human HEV in sequence variation. No evidence for the transmission of bat hepeviruses to humans was found in over 90,000 human blood donations and individual patient sera. Full-genome analysis of one representative virus confirmed formal classification within the family Hepeviridae. Sequence- and distance-based taxonomic evaluations suggested that bat hepeviruses constitute a distinct genus within the family Hepeviridae and that at least three other genera comprising human, rodent, and avian hepeviruses can be designated. This may imply that hepeviruses invaded mammalian hosts nonrecently and underwent speciation according to their host restrictions. Human HEV-related viruses in farmed and peridomestic animals might represent secondary acquisitions of human viruses, rather than animal precursors causally involved in the evolution of human HEV.

Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs.