Sébastien Calvignac-Spencer

A Novel Human Polyomavirus Closely Related to the African Green Monkey-Derived Lymphotropic Polyomavirus

ABSTRACT We identified a novel human polyomavirus from a kidney transplant patient under immunosuppressive treatment, by use of a generic PCR. The genome of the virus was completely amplified and sequenced. In phylogenetic analyses, it appeared as the closest relative to the African green monkey-derived lymphotropic polyomavirus (LPV). Further investigation of clinical samples from immunocompromised patients with specific nested PCR revealed additional positive samples, indicating that the virus naturally infects humans. The virus was tentatively named human polyomavirus 9 (HPyV9). The previously observed seroreactivity to LPV in human populations might find a partial explanation in the circulation of HPyV9.

Investigating the zoonotic origin of the West African Ebola epidemic

The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2‐year‐old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free‐tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology.

Identification of a Novel Human Polyomavirus in Organs of the Gastrointestinal Tract

Polyomaviruses are small, non-enveloped viruses with a circular double-stranded DNA genome. Using a generic polyomavirus PCR targeting the VP1 major structural protein gene, a novel polyomavirus was initially identified in resected human liver tissue and provisionally named Human Polyomavirus 12 (HPyV12). Its 5033 bp genome is predicted to encode large and small T antigens and the 3 structural proteins VP1, VP2 and VP3. Phylogenetic analyses did not reveal a close relationship to any known human or animal polyomavirus. Investigation of organs, body fluids and excretions of diseased individuals and healthy subjects with both HPyV12-specific nested PCR and quantitative real-time PCR revealed additional virus-positive samples of resected liver, cecum and rectum tissues and a positive fecal sample. A capsomer-based IgG ELISA was established using the major capsid protein VP1 of HPyV12. Seroprevalences of 23% and 17%, respectively, were determined in sera from healthy adults and adolescents and a pediatric group of children. These data indicate that the virus naturally infects humans and that primary infection may already occur in childhood.

Wild great apes as sentinels and sources of infectious disease

Emerging zoonotic infectious diseases pose a serious threat to global health. This is especially true in relation to the great apes, whose close phylogenetic relationship with humans results in a high potential for microorganism exchange. In this review, we show how studies of the microorganisms of wild great apes can lead to the discovery of novel pathogens of importance for humans. We also illustrate how these primates, living in their natural habitats, can serve as sentinels for outbreaks of human disease in regions with a high likelihood of disease emergence. Greater sampling efforts and improvements in sample preservation and diagnostic capacity are rapidly improving our understanding of the diversity and distribution of microorganisms in wild great apes. Linking non-invasive diagnostic data with observational health data from great apes habituated to human presence is a promising approach for the discovery of pathogens of high relevance for humans.

One Hundred Twenty Years of Koala Retrovirus Evolution Determined from Museum Skins

Although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (KoRV) is the only retrovirus known to be currently invading the germ line of its host. KoRV is believed to have first infected koalas in northern Australia less than two centuries ago. We examined KoRV in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern Australian specimens. Strikingly, KoRV env sequences were conserved among koalas collected over the span of a century, and two functional motifs that affect viral infectivity were fixed across the museum koala specimens. We detected only 20 env polymorphisms among the koalas, likely representing derived mutations subject to purifying selection. Among northern Australian koalas, KoRV was already ubiquitous by the late 19th century, suggesting that KoRV evolved and spread among koala populations more slowly than previously believed. Given that museum and modern koalas share nearly identical KoRV sequences, it is likely that koala populations, for more than a century, have experienced increased susceptibility to diseases caused by viral pathogenesis.

A taxonomy update for the family Polyomaviridae

Many distinct polyomaviruses infecting a variety of vertebrate hosts have recently been discovered, and their complete genome sequence could often be determined. To accommodate this fast-growing diversity, the International Committee on Taxonomy of Viruses (ICTV) Polyomaviridae Study Group designed a host- and sequence-based rationale for an updated taxonomy of the family Polyomaviridae. Applying this resulted in numerous recommendations of taxonomical revisions, which were accepted by the Executive Committee of the ICTV in December 2015. New criteria for definition and creation of polyomavirus species were established that were based on the observed distance between large T antigen coding sequences. Four genera (Alpha-, Beta, Gamma- and Deltapolyomavirus) were delineated that together include 73 species. Species naming was made as systematic as possible – most species names now consist of the binomial name of the host species followed by polyomavirus and a number reflecting the order of discovery. It is hoped that this important update of the family taxonomy will serve as a stable basis for future taxonomical developments.

Novel mycobacterium tuberculosis complex isolate from a wild chimpanzee

Tuberculosis (TB) is caused by gram-positive bacteria known as the Mycobacterium tuberculosis complex (MTBC). MTBC include several human-associated lineages and several variants adapted to domestic and, more rarely, wild animal species. We report an M. tuberculosis strain isolated from a wild chimpanzee in Côte d’Ivoire that was shown by comparative genomic and phylogenomic analyses to belong to a new lineage of MTBC, closer to the human-associated lineage 6 (also known as M. africanum West Africa 2) than to the other classical animal-associated MTBC strains. These results show that the general view of the genetic diversity of MTBC is limited and support the possibility that other MTBC variants exist, particularly in wild mammals in Africa. Exploring this diversity is crucial to the understanding of the biology and evolutionary history of this widespread infectious disease.

Evidence for continuing cross-species transmission of SIVsmm to humans: characterization of a new HIV-2 lineage in rural Côte d'Ivoire.

HIV types 1 and 2 (HIV-1 and HIV-2) are the result of multiple cross-species transmissions of their simian counterparts (SIVs) to humans. We studied whether new SIVs lineages have been transmitted to humans in rural Côte d’Ivoire and identified a novel HIV-2 variant (HIV-2-07IC-TNP03) not related to any of the previously defined HIV-2 groups. This finding shows that sooty mangabey viruses continue to be transmitted to humans, causing new zoonotic outbreaks.

Assessing the Evidence Supporting Fruit Bats as the Primary Reservoirs for Ebola Viruses.

Since their discovery 40 years ago, Ebola viruses (in the following: EBOV; family Filoviridae, genus Ebolavirus) continue to emerge unpredictably and cause Ebola virus disease (EVD) in humans and susceptible animals in tropical Africa (Leroy et al. 2004; Feldmann and Geisbert 2011). The scale of the current epidemic in West Africa demonstrates the impact that a single spillover event can have (Baize et al. 2014; Gire et al. 2014). Meanwhile, the reservoir(s) and ecology of EBOV remain largely unknown (Groseth et al. 2007; Feldmann and Geisbert 2011), hampering prediction of future outbreaks. To date, the only laboratory-confirmed sources of human EVD outbreaks were infected great apes and duikers (Leroy et al. 2004). However, these species are unlikely reservoirs as high mortality rates rule out an indefinite infection chain (Leroy et al. 2004; Bermejo et al. 2006; Wittmann et al. 2007). Scientists are therefore searching for other hosts where EBOV circulate without major negative effects; fruit bats have received the most research attention and are frequently referred to as the reservoir for African EBOV (Centers for Disease Control and Prevention 2014b; O’Shea et al. 2014; World Health Organization 2014). We review current evidence and highlight that fruit bats may not represent the main, or the sole, reservoir. We discuss evidence implicating insectivorous bats and reiterate that bats themselves might not be the ultimate reservoir for EBOV. Knowing which species are involved will facilitate an understanding of factors allowing spillover to susceptible human and wildlife populations (Viana et al. 2014; Plowright et al. 2015).

iDNA from terrestrial haematophagous leeches as a wildlife surveying and monitoring tool – prospects, pitfalls and avenues to be developed

Invertebrate-derived DNA (iDNA) from terrestrial haematophagous leeches has recently been proposed as a powerful non-invasive tool with which to detect vertebrate species and thus to survey their populations. However, to date little attention has been given to whether and how this, or indeed any other iDNA-derived data, can be combined with state-of-the-art analytical tools to estimate wildlife abundances, population dynamics and distributions. In this review, we discuss the challenges that face the application of existing analytical methods such as site-occupancy and spatial capture-recapture (SCR) models to terrestrial leech iDNA, in particular, possible violations of key assumptions arising from factors intrinsic to invertebrate parasite biology. Specifically, we review the advantages and disadvantages of terrestrial leeches as a source of iDNA and summarize the utility of leeches for presence, occupancy, and spatial capture-recapture models. The main source of uncertainty that attends species detections derived from leech gut contents is attributable to uncertainty about the spatio-temporal sampling frame, since leeches retain host-blood for months and can move after feeding. Subsequently, we briefly address how the analytical challenges associated with leeches may apply to other sources of iDNA. Our review highlights that despite the considerable potential of leech (and indeed any) iDNA as a new survey tool, further pilot studies are needed to assess how analytical methods can overcome or not the potential biases and assumption violations of the new field of iDNA. Specifically we argue that studies to compare iDNA sampling with standard survey methods such as camera trapping, and those to improve our knowledge on leech (and other invertebrate parasite) physiology, taxonomy, and ecology will be of immense future value.