Bat coronaviruses related to SARS-CoV-2 and infectious for human cells.

The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats1-4, including the closest virus from R. affinis, RaTG13 (refs. 5,6), and pangolins7-9. SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range10-12. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.

Discovery and Genomic Characterization of a Novel Henipavirus, Angavokely Virus, from Fruit Bats in Madagascar.

The genus Henipavirus (family Paramyxoviridae) currently comprises seven viruses, four of which have demonstrated prior evidence of zoonotic capacity. These include the biosafety level 4 agents Hendra (HeV) and Nipah (NiV) viruses, which circulate naturally in pteropodid fruit bats. Here, we describe and characterize Angavokely virus (AngV), a divergent henipavirus identified in urine samples from wild, Madagascar fruit bats. We report the nearly complete 16,740-nucleotide genome of AngV, which encodes the six major henipavirus structural proteins (nucleocapsid, phosphoprotein, matrix, fusion, glycoprotein, and L polymerase). Within the phosphoprotein (P) gene, we identify an alternative start codon encoding the AngV C protein and a putative mRNA editing site where the insertion of one or two guanine residues encodes, respectively, additional V and W proteins. In other paramyxovirus systems, C, V, and W are accessory proteins involved in antagonism of host immune responses during infection. Phylogenetic analysis suggests that AngV is ancestral to all four previously described bat henipaviruses-HeV, NiV, Cedar virus (CedV), and Ghanaian bat virus (GhV)-but evolved more recently than rodent- and shrew-derived henipaviruses, Mojiang (MojV), Gamak (GAKV), and Daeryong (DARV) viruses. Predictive structure-based alignments suggest that AngV is unlikely to bind ephrin receptors, which mediate cell entry for all other known bat henipaviruses. Identification of the AngV receptor is needed to clarify the virus's potential host range. The presence of V and W proteins in the AngV genome suggest that the virus could be pathogenic following zoonotic spillover. IMPORTANCE Henipaviruses include highly pathogenic emerging zoonotic viruses, derived from bat, rodent, and shrew reservoirs. Bat-borne Hendra (HeV) and Nipah (NiV) are the most well-known henipaviruses, for which no effective antivirals or vaccines for humans have been described. Here, we report the discovery and characterization of a novel henipavirus, Angavokely virus (AngV), isolated from wild fruit bats in Madagascar. Genomic characterization of AngV reveals all major features associated with pathogenicity in other henipaviruses, suggesting that AngV could be pathogenic following spillover to human hosts. Our work suggests that AngV is an ancestral bat henipavirus that likely uses viral entry pathways distinct from those previously described for HeV and NiV. In Madagascar, bats are consumed as a source of human food, presenting opportunities for cross-species transmission. Characterization of novel henipaviruses and documentation of their pathogenic and zoonotic potential are essential to predicting and preventing the emergence of future zoonoses that cause pandemics.

ICTV Virus Taxonomy Profile: Herpesviridae 2021.

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.

DNA Polymerase Sequences of New World Monkey Cytomegaloviruses: Another Molecular Marker with Which To Infer Platyrrhini Systematics.

Over the past few decades, a large number of studies have identified herpesvirus sequences from many mammalian species around the world. Among the different nonhuman primate species tested so far for cytomegaloviruses (CMVs), only a few were from the New World. Seeking to identify CMV homologues in New World monkeys (NWMs), we carried out molecular screening of 244 blood DNA samples from 20 NWM species from Central and South America. Our aim was to reach a better understanding of their evolutionary processes within the Platyrrhini parvorder. Using PCR amplification with degenerate consensus primers targeting highly conserved amino acid motifs encoded by the herpesvirus DNA polymerase gene, we characterized novel viral sequences from 12 species belonging to seven genera representative of the three NWM families. BLAST searches, pairwise nucleotide and amino acid sequence comparisons, and phylogenetic analyses confirmed that they all belonged to the Cytomegalovirus genus. Previously determined host taxa allowed us to demonstrate a good correlation between the distinct monophyletic clades of viruses and those of the infected primates at the genus level. In addition, the evolutionary branching points that separate NWM CMVs were congruent with the divergence dates of their hosts at the genus level. These results significantly expand our knowledge of the host range of this viral genus and strongly support the occurrence of cospeciation between these viruses and their hosts. In this respect, we propose that NWM CMV DNA polymerase gene sequences may serve as reliable molecular markers with which to infer Platyrrhini phylogenetics.IMPORTANCE Investigating evolutionary processes between viruses and nonhuman primates has led to the discovery of a large number of herpesviruses. No study published so far on primate cytomegaloviruses has extensively studied New World monkeys (NWMs) at the subspecies, species, genus, and family levels. The present study sought to identify cytomegalovirus homologues in NWMs and to decipher their evolutionary relationships. This led us to characterize novel viruses from 12 of the 20 primate species tested, which are representative of the three NWM families. The identification of distinct viruses in these primates not only significantly expands our knowledge of the host range of this viral genus but also sheds light on its evolutionary history. Phylogenetic analyses and molecular dating of the sequences obtained support a virus-host coevolution.

Maripa Virus RNA Load and Antibody Response in Hantavirus Pulmonary Syndrome, French Guiana.

We report viral RNA loads and antibody responses in 6 severe human cases of Maripa virus infection (2 favorable outcomes) and monitored both measures during the 6-week course of disease in 1 nonfatal case. Further research is needed to determine prevalence of this virus and its effect on other hantaviruses.

How Social Structure Drives the Population Dynamics of the Common Vampire Bat (Desmodus rotundus, Phyllostomidae).

Social systems are major drivers of population structure and gene flow, with important effects on dynamics and dispersal of associated populations of parasites. Among bats, the common vampire bat (Desmodus rotundus) has likely one of the most complex social structures. Using autosomal and mitochondrial markers on vampires from Mexico, French Guiana, and North Brazil, from both roosting and foraging areas, we observed an isolation by distance at the wider scale and lower but significant differentiation between closer populations (<50 km). All populations had a low level of relatedness and showed deviations from Hardy-Weinberg equilibrium and a low but significant inbreeding coefficient. The associated heterozygote deficiency was likely related to a Wahlund effect and to cryptic structures, reflecting social groups living in syntopy, both in roosting and foraging areas, with only limited admixture. Discrepancy between mitochondrial and nuclear markers suggests female philopatry and higher dispersal rates in males, associated with peripheral positions in the groups. Vampires are also the main neotropical reservoir for rabies virus, one of the main lethal pathogens for humans. Female social behaviors and trophallaxis may favor a rapid spread of virus to related and unrelated offspring and females. The high dispersal capacity of males may explain the wider circulation of viruses and the inefficacy of bat population controls. In such opportunistic species, gene connectivity should be considered for management decision making. Strategies such as culling could induce immigration of bats from neighboring colonies to fill vacant roosts and feeding areas, associated with the dispersal of viral strains.

Predictors of abnormal cytology among HPV-infected women in remote territories of French Guiana.

BACKGROUND: Cervical cancer prevention using cervical cytology is insufficiently sensitive, a significant proportion of HPV-infected women having normal cytology. The objective of the present study was to try to identify factors associated with abnormal cytology in HPV-infected women living in remote areas of French Guiana. METHODS: A study was conducted in women aged 20-65 years having HPV infections confirmed by HPV DNA detection using the GREINER-BIO-ONE kit. In addition to HPV testing, cytology was performed and classified as normal or abnormal. Demographic and life history variables, and infecting genotypes were compared between the normal and abnormal cytology groups. RESULTS: None of the demographic and life history variables were associated with cytology results. HPV genotype 53 was significantly associated with absence of cytological abnormalities whereas HPV 52, 58, 16 and perhaps 33 and 66 were independently associated with a greater risk of cytological abnormalities. When grouping HPV genotypes in different species, only species 9 (HPV 16, 31, 33, 35, 52, 58, 67) was significantly associated with abnormal cytology AOR = 5.1 (95% CI = 2.3-11.2), P < 0.001. CONCLUSIONS: It was not possible to predict which HPV-infected women will have cytological abnormalities or notfrom anamnesis. In this study HPV 53 seemed more benign than other HPV genotypes. On the contrary, species n°9, containing 5 of the genotypes contained in the nonavalent HPV vaccine, was significantly associated with more cytological abnormalities. HPV testing and vaccination with the nonavalent vaccine should be implemented in these remote parts of French Guiana.

Hantavirus Pulmonary Syndrome Caused by Maripa Virus in French Guiana, 2008-2016.

We report 5 human cases of hantavirus pulmonary syndrome found during surveillance in French Guiana in 2008-2016; of the 5 patients, 4 died. This pathogen should continue to be monitored in humans and rodents in effort to reduce the occurrence of these lethal infections in humans stemming from ecosystem disturbances.

Absence of vaccinia virus detection in a remote region of the Northern Amazon forests, 2005-2015.

Vaccinia virus (VACV) circulates in Brazil and other South America countries and is responsible for a zoonotic disease that usually affects dairy cattle and humans, causing economic losses and impacting animal and human health. Furthermore, it has been detected in wild areas in the Brazilian Amazon. To better understand the natural history of VACV, we investigated its circulation in wildlife from French Guiana, a remote region in the Northern Amazon forest. ELISA and plaque reduction neutralization tests were performed to detect anti-orthopoxvirus antibodies. Real-time and standard PCR targeting C11R, A56R and A26L were applied to detect VACV DNA in serum, saliva and tissue samples. No evidence of VACV infection was found in any of the samples tested. These findings provide additional information on the VACV epidemiological puzzle. The virus could nevertheless be circulating at low levels that were not detected in areas where no humans or cattle are present.

The singular epidemiology of HPV infection among French Guianese women with normal cytology.

BACKGROUND: In French Guiana, cervical cancer is the second most frequent cancer in females. The objective of the present study was to describe the prevalence of HPV infections in women with normal cervical cytology living in the remote villages of French Guiana. METHODS: Before the study, the study team communicated in the remote villages on the importance of screening. All women from the target population were offered to participate. They signed informed consent during inclusion and then had a concomitant HPV-test and cervical smear. Only women with normal cytology and a good quality smear were analyzed. The detection of HPV-DNA was performed using the GREINER-BIO-ONE kit. RESULTS: Overall, 27.2% of women with normal cervical cytology had a positive HPV-test. There was a U-shaped evolution of prevalence with women over 50 years having the highest HPV prevalence, followed by the 20 to 29 years group. The most prevalent HPV genotypes were HPV 53(3.52%), 68(3.33%), 52(2.59%), 31(2.22%) and 16 (1.85%). The proportion of HPV 16 among HPV-infected women was 6.8%. CONCLUSIONS: HPV prevalence in cytologically normal women was very high. The most prevalent genotypes were very different from what is usually described in the world, and notably in South America.

Virus hébergés par les rongeurs en Guyane française.

Among mammals, rodents play a key role in the emergence of viral diseases. In French Guiana, with 36 rodent species recorded in various ecosystems (pristine forests, savannas, anthropized environments), some natural habitats today encounter anthropogenic perturbations that induce changes in community structure and population dynamics. These modifications are sometimes associated with the circulation and emergence of viral pathogens. For 10 years, investigations on the circulation of two rodent-borne viruses, Hantavirus and Mammarenavirus, are underway in rodent populations as well as in humans for hantavirus. These investigations identified viruses from both genera in their potential reservoirs and allow describing the most favourable habitats for the reservoirs of hantavirus where the risk of viral emergence may be higher. We suggest to investigate how anthropic perturbations in rodent communities can drive the emergence of viruses that are currently confined to a small scale and search for evidence of infection in the human population.

Rodent-borne viruses in French Guiana.

Among mammals, rodents play a key role in the emergence of viral diseases. In French Guiana, with 36 rodent species recorded in various ecosystems (pristine forests, savannas, anthropized environments), some natural habitats today encounter anthropogenic perturbations that induce changes in community structure and population dynamics. These modifications are sometimes associated with the circulation and emergence of viral pathogens. For 10 years, investigations on the circulation of two rodent-borne viruses, Hantavirus and Mammarenavirus, are underway in rodent populations as well as in humans for hantavirus. These investigations identified viruses from both genera in their potential reservoirs and allow describing the most favourable habitats for the reservoirs of hantavirus where the risk of viral emergence may be higher. We suggest to investigate how anthropic perturbations in rodent communities can drive the emergence of viruses that are currently confined to a small scale and search for evidence of infection in the human population.

Spatial pattern of genetic diversity and selection in the MHC class II DRB of three Neotropical bat species.

BACKGROUND: Although bats are natural reservoirs of many pathogens, few studies have been conducted on the genetic variation and detection of selection in major histocompatibility complex (MHC) genes. These genes are critical for resistance and susceptibility to diseases, and host-pathogen interactions are major determinants of their extensive polymorphism. Here we examined spatial patterns of diversity of the expressed MHC class II DRB gene of three sympatric Neotropical bats, Carollia perspicillata and Desmodus rotundus (Phyllostomidae), and Molossus molossus (Molossidae), all of which use the same environments (e.g., forests, edge habitats, urban areas). Comparison with neutral marker (mtDNA D-loop) diversity was performed at the same time. RESULTS: Twenty-three DRB alleles were identified in 19 C. perspicillata, 30 alleles in 35 D. rotundus and 20 alleles in 28 M. molossus. The occurrence of multiple DRB loci was found for the two Phyllostomidae species. The DRB polymorphism was high in all sampling sites and different signatures of positive selection were detected depending on the environment. The patterns of DRB diversity were similar to those of neutral markers for C. perspicillata and M. molossus. In contrast, these patterns were different for D. rotundus for which a geographical structure was highlighted. A heterozygote advantage was also identified for this species. No recombination or gene conversion event was found and phylogenetic relationships showed a trans-species mode of evolution in the Phyllostomids. CONCLUSIONS: This study of MHC diversity demonstrated the strength of the environment and contrasting pathogen pressures in shaping DRB diversity. Differences between positively selected sites identified in bat species highlighted the potential role of gut microbiota in shaping immune responses. Furthermore, multiple geographic origins and/or population admixtures observed in C. perspicillata and M. molossus populations acted as an additional force in shaping DRB diversity. In contrast, DRB diversity of D. rotundus was shaped by environment rather than demographic history.

African great apes are naturally infected with roseoloviruses closely related to human herpesvirus 7.

UNLABELLED: Primates are naturally infected with herpesviruses. During the last 15 years, the search for homologues of human herpesviruses in nonhuman primates allowed the identification of numerous viruses belonging to the different herpesvirus subfamilies and genera. No simian homologue of human herpesvirus 7 (HHV7) has been reported to date. To investigate the putative existence of HHV7-like viruses in African great apes, we applied the consensus-degenerate hybrid oligonucleotide primers (CODEHOP) program-mediated PCR strategy to blood DNA samples from the four common chimpanzee subspecies (Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii), pygmy chimpanzees (Pan paniscus), as well as lowland gorillas (Gorilla gorilla gorilla). This study led to the discovery of a novel roseolovirus close to HHV7 in each of these nonhuman primate species and subspecies. Generation of the partial glycoprotein B (1,111-bp) and full-length DNA polymerase (3,036/3,042-bp) gene sequences allowed the deciphering of their evolutionary relationships. Phylogenetic analyses revealed that HHV7 and its African great ape homologues formed well-supported monophyletic lineages whose topological resemblance to the host phylogeny is suggestive of virus-host codivergence. Notably, the evolutionary branching points that separate HHV7 from African great ape herpesvirus 7 are remarkably congruent with the dates of divergence of their hosts. Our study shows that African great apes are hosts of human herpesvirus homologues, including HHV7 homologues, and that the latter, like other DNA viruses that establish persistent infections, have cospeciated with their hosts. IMPORTANCE: Human herpesviruses are known to possess simian homologues. However, surprisingly, none has been identified to date for human herpesvirus 7 (HHV7). This study is the first to describe simian homologues of HHV7. The extensive search performed on almost all African great ape species and subspecies, i.e., common chimpanzees of the four subspecies, bonobos, and lowland gorillas, has allowed characterization of a specific virus in each. Genetic characterization of the partial glycoprotein B and full-length DNA polymerase gene sequences, followed by their phylogenetic analysis and estimation of divergence times, has shed light on the evolutionary relationships of these viruses. In this respect, we conclusively demonstrate the cospeciation between these new viruses and their hosts and report cases of cross-species transmission between two common chimpanzee subspecies in both directions.

An Entomological Investigation during a Recent Rift Valley Fever Epizootic/Epidemic Reveals New Aspects of the Vectorial Transmission of the Virus in Madagascar.

A Rift Valley fever (RVF) outbreak occurred in at least five regions of Madagascar in 2021. The aim of this study was to provide an overview of the richness, abundance, ecology, and trophic preferences of mosquitoes in the Mananjary district and to investigate the distribution of mosquitoes that were RT-PCR-positive for RVFV. Three localities were prospected from 26 April to 4 May 2021, using light traps, BG-Sentinel traps baited with an artificial human odor, Muirhead-Thomson pit traps, and indoor pyrethroid spray catches. A total of 2806 mosquitoes belonging to at least 26 species were collected. Of 512 monospecific pools of mosquitoes tested with real-time RT-PCR, RVFV was detected in 37 pools representing 10 mosquito species. The RVFV-positive species were as follows: Aedes albopictus, Ae. argenteopunctatus, Anopheles coustani, An. gambiae s.l., An. mascarensis, An. squamosus/cydippis, Culex antennatus, Cx. decens, Cx. Tritaeniorhynchus, and Uranotaenia spp. Of the 450 tested engorged females, 78.7% had taken a blood meal on humans, 92.9% on cattle, and 71.6% had taken mixed (human-cattle) blood meals. This investigation suggests the potential role of mosquitoes in RVFV transmission within this epizootic/epidemic context and that the human populations at the three study sites were highly exposed to mosquitoes. Therefore, the use of impregnated mosquito nets as an appropriate prevention method is recommended.

The Re-Emergence of Rift Valley Fever in Mananjary District, Madagascar in 2021: A Call for Action.

An epizootic of rift valley fever (RVF) was suspected on 21 February 2021 in various districts of Madagascar, with a lab confirmation on 1 April 2021. A cross-sectional survey aiming to detect cases of RVF in humans and to study the circulation of rift valley fever virus (RVFV) in animals was conducted from 22 April to 4 May 2021 in the district of Mananjary. Blood samples from cattle and humans were tested using serological and molecular techniques. In cattle, the circulation of RVFV was confirmed between 5 February and 4 May 2021. The positivity rates of anti-RVFV IgG and IgM were 60% and 40%, respectively. In humans, the circulation of RVFV was observed from 1 April to 5 May 2021. The positivity rate of RVFV was estimated to be 11.7% by combining the results of the molecular and serological approaches. Of the 103 individuals who agreed to participate in the survey, 3 were determined to be positive by RT-PCR, and 10 had anti-RVFV IgM. Among them, one was positive for both. Given that previous studies have reported the circulation of RVFV during inter-epidemic periods and the occurrence of outbreaks due to imported RVFV in Madagascar, our findings suggest the importance of strengthening RVF surveillance from a "One Health" perspective by conducting syndromic and risk-based surveillance at the national and regional levels.

Antiretroviral therapy promotes an inflammatory-like pattern of human T-cell lymphotropic virus type 1 (HTLV-1) replication in human immunodeficiency virus type 1/HTLV-1 co-infected individuals.

Upon antiretroviral therapy (ART) human immunodeficiency virus (HIV)/human T-cell lymphotropic virus type 1 (HTLV-1) co-infected individuals frequently develop neurological disorders through hitherto unknown mechanisms. Here, we show that effective anti-HIV ART increases HTLV-1 proviral load through a polyclonal integration pattern of HTLV-1 in both CD4(+) and CD8(+) T-cell subsets that is reminiscent of that typically associated with HTLV-1-related inflammatory conditions. These data indicate that preventing ART-triggered clonal expansion of HTLV-1-infected cells in co-infected individuals deserves investigation.

Complete genome sequence of a novel hantavirus variant of Rio Mamoré virus, Maripa virus, from French Guiana.

We report the first complete genome sequence of Maripa virus identified in 2009 from a patient with hantavirus pulmonary syndrome in French Guiana. Maripa virus corresponds to a new variant of the Rio Mamoré virus species in the Bunyaviridae family, genus Hantavirus.

Factors Associated with Carriage of Enteropathogenic and Non-Enteropathogenic Viruses: A Reanalysis of Matched Case-Control Data from the AFRIBIOTA Site in Antananarivo, Madagascar.

Environmental Enteric Dysfunction (EED) is an associate driver of stunting in poor settings, and intestinal infections indirectly contribute to the pathophysiology underlying EED. Our work aimed at assessing whether enteric viral carriage is determinant to stunting. A total of 464 healthy and asymptomatic children, aged 2 to 5 years, were recruited, and classified as non-stunted, moderately stunted, or severely stunted. Among the recruited children, 329 stool samples were obtained and screened for enteric and non-enteric viruses by real-time polymerase chain reaction. We statistically tested for the associations between enteric viral and potential risk factors. Approximately 51.7% of the stool samples were positive for at least one virus and 40.7% were positive for non-enteric adenoviruses. No statistical difference was observed between virus prevalence and the growth status of the children. We did not find any statistically significant association between viral infection and most of the socio-demographic risk factors studied, except for having an inadequate food quality score or an over-nourished mother. In addition, being positive for Ascaris lumbricoides was identified as a protective factor against viral infection. In conclusion, we did not find evidence of a direct link between stunting and enteropathogenic viral carriage in our population.