Mpox outbreak in Rio de Janeiro, Brazil: A translational approach.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

Reservoir host immunology and life history shape virulence evolution in zoonotic viruses.

The management of future pandemic risk requires a better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Meta-analyses suggest that the virulence of emerging zoonoses is correlated with but not completely predictable from reservoir host phylogeny, indicating that specific characteristics of reservoir host immunology and life history may drive the evolution of viral traits responsible for cross-species virulence. In particular, bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, a phenomenon that cannot be explained by phylogenetic distance alone. In order to disentangle the fundamental drivers of these patterns, we develop a nested modeling framework that highlights mechanisms that underpin the evolution of viral traits in reservoir hosts that cause virulence following cross-species emergence. We apply this framework to generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, recapturing trends in virus-induced human mortality rates reported in the literature. Notably, our work offers a mechanistic hypothesis to explain the extreme virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, viral tolerance, and constitutive immunity impact the evolution of viral traits that cause virulence following spillover to humans. Our theoretical framework offers a series of testable questions and predictions designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts.

Virus diversity, wildlife-domestic animal circulation and potential zoonotic viruses of small mammals, pangolins and zoo animals.

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.

No Substantial Histopathologic Changes in Mops condylurus Bats Naturally Infected with Bombali Virus, Kenya.

We found similar mild perivascular inflammation in lungs of Bombali virus-positive and -negative Mops condylurus bats in Kenya, indicating the virus is well-tolerated. Our findings indicate M. condylurus bats may be a reservoir host for Bombali virus. Increased surveillance of these bats will be important to reduce potential virus spread.

Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models.

To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

Structural Bases of Zoonotic and Zooanthroponotic Transmission of SARS-CoV-2.

The emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of possible animal-to-human (zoonotic) and human-to-animal (zooanthroponotic) transmission and potential spread within animal species. A range of animal species have been verified for SARS-CoV-2 susceptibility, either in vitro or in vivo. However, the molecular bases of such a broad host spectrum for the SARS-CoV-2 remains elusive. Here, we structurally and genetically analysed the interaction between the spike protein, with a particular focus on receptor binding domains (RBDs), of SARS-CoV-2 and its receptor angiotensin-converting enzyme 2 (ACE2) for all conceivably susceptible groups of animals to gauge the structural bases of the SARS-CoV-2 host spectrum. We describe our findings in the context of existing animal infection-based models to provide a foundation on the possible virus persistence in animals and their implications in the future eradication of COVID-19.

Multiple spillovers from humans and onward transmission of SARS-CoV-2 in white-tailed deer.

Many animal species are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and could act as reservoirs; however, transmission in free-living animals has not been documented. White-tailed deer, the predominant cervid in North America, are susceptible to SARS-CoV-2 infection, and experimentally infected fawns can transmit the virus. To test the hypothesis that SARS-CoV-2 is circulating in deer, 283 retropharyngeal lymph node (RPLN) samples collected from 151 free-living and 132 captive deer in Iowa from April 2020 through January of 2021 were assayed for the presence of SARS-CoV-2 RNA. Ninety-four of the 283 (33.2%) deer samples were positive for SARS-CoV-2 RNA as assessed by RT-PCR. Notably, following the November 2020 peak of human cases in Iowa, and coinciding with the onset of winter and the peak deer hunting season, SARS-CoV-2 RNA was detected in 80 of 97 (82.5%) RPLN samples collected over a 7-wk period. Whole genome sequencing of all 94 positive RPLN samples identified 12 SARS-CoV-2 lineages, with B.1.2 (n = 51; 54.5%) and B.1.311 (n = 19; 20%) accounting for ∼75% of all samples. The geographic distribution and nesting of clusters of deer and human lineages strongly suggest multiple human-to-deer transmission events followed by subsequent deer-to-deer spread. These discoveries have important implications for the long-term persistence of the SARS-CoV-2 pandemic. Our findings highlight an urgent need for a robust and proactive "One Health" approach to obtain enhanced understanding of the ecology, molecular evolution, and dissemination of SARS-CoV-2.

Spatiotemporal distribution, abundance, and host interactions of two invasive vectors of arboviruses, Aedes albopictus and Aedes japonicus, in Pennsylvania, USA.

BACKGROUND: Aedes albopictus and Aedes japonicus, two invasive mosquito species in the United States, are implicated in the transmission of arboviruses. Studies have shown interactions of these two mosquito species with a variety of vertebrate hosts; however, regional differences exist and may influence their contribution to arbovirus transmission. METHODS: We investigated the distribution, abundance, host interactions, and West Nile virus infection prevalence of Ae. albopictus and Ae. japonicus by examining Pennsylvania mosquito and arbovirus surveillance data for the period between 2010 and 2018. Mosquitoes were primarily collected using gravid traps and BG-Sentinel traps, and sources of blood meals were determined by analyzing mitochondrial cytochrome b gene sequences amplified in PCR assays. RESULTS: A total of 10,878,727 female mosquitoes representing 51 species were collected in Pennsylvania over the 9-year study period, with Ae. albopictus and Ae. japonicus representing 4.06% and 3.02% of all collected mosquitoes, respectively. Aedes albopictus was distributed in 39 counties and Ae. japonicus in all 67 counties, and the abundance of these species increased between 2010 and 2018. Models suggested an increase in the spatial extent of Ae. albopictus during the study period, while that of Ae. japonicus remained unchanged. We found a differential association between the abundance of the two mosquito species and environmental conditions, percent development, and median household income. Of 110 Ae. albopictus and 97 Ae. japonicus blood meals successfully identified to species level, 98% and 100% were derived from mammalian hosts, respectively. Among 12 mammalian species, domestic cats, humans, and white-tailed deer served as the most frequent hosts for the two mosquito species. A limited number of Ae. albopictus acquired blood meals from avian hosts solely or in mixed blood meals. West Nile virus was detected in 31 pools (n = 3582 total number of pools) of Ae. albopictus and 12 pools (n = 977 total pools) of Ae. japonicus. CONCLUSIONS: Extensive distribution, high abundance, and frequent interactions with mammalian hosts suggest potential involvement of Ae. albopictus and Ae. japonicus in the transmission of human arboviruses including Cache Valley, Jamestown Canyon, La Crosse, dengue, chikungunya, and Zika should any of these viruses become prevalent in Pennsylvania. Limited interaction with avian hosts suggests that Ae. albopictus might occasionally be involved in transmission of arboviruses such as West Nile in the region.

Seroprevalence of Pteropine orthoreovirus in humans remain similar after nearly two decades (2001-2002 vs. 2017) in Tioman Island, Malaysia.

Pteropine orthoreovirus (PRV) is an emerging zoonotic respiratory virus that can be transmitted from bats to humans. In Malaysia, aside from PRV2P (Pulau virus) being isolated from Pteropus hypomelanus sampled in Tioman Island, PRV3M (Melaka virus), PRV4K (Kampar virus), and PRV7S (Sikamat virus) were all isolated from samples of patients who reported having a disease spectrum from acute respiratory distress to influenza-like illness and sometimes even with enteric symptoms such as diarrhea and abdominal pain. Screening of sera collected from human volunteers on Tioman Island in 2001-2002 demonstrated that 12.8% (14/109) were positive for PRV2P and PRV3M. Taking all these together, we aim to investigate the serological prevalence of PRV (including PRV4K and PRV7S) among Tioman Island inhabitants again with the assumption that the seroprevalence rate will remain nearly similar to the above reported if human exposure to bats is still happening in the island. Using sera collected from human volunteers on the same island in 2017, we demonstrated seroprevalence of 17.8% (28/157) against PRV2P and PRV3M, respectively. Seropositivity of 11.4% among Tioman Island inhabitants against PRV4K and PRV7S, respectively, was described in this study. In addition, the seroprevalence of 89.5% (17/19), 73.6% (14/19), 63.0% (12/19), and 73.6% (14/19) against PRV2P, PRV3M, PRV4K, and PRV7S, respectively, were observed among pteropid bats in the island. We revealed that the seroprevalence of PRV among island inhabitants remains nearly similar after nearly two decades, suggesting that potential spill-over events in bat-human interface areas in the Tioman Island. We are unclear whether such spillover was directly from bats to humans, as suspected for the PRV3M human cases, or from an intermediate host(s) yet to be identified. There is a high possibility of the viruses circulating among the bats as demonstrated by high seroprevalence against PRV in the bats.

Functional binding dynamics relevant to the evolution of zoonotic spillovers in endemic and emergent Betacoronavirus strains.

Comparative functional analysis of the dynamic interactions between various Betacoronavirus mutant strains and broadly utilized target proteins such as ACE2 and CD26, is crucial for a more complete understanding of zoonotic spillovers of viruses that cause diseases such as COVID-19. Here, we employ machine learning to replicated sets of nanosecond scale GPU accelerated molecular dynamics simulations to statistically compare and classify atom motions of these target proteins in both the presence and absence of different endemic and emergent strains of the viral receptor binding domain (RBD) of the S spike glycoprotein. A multi-agent classifier successfully identified functional binding dynamics that are evolutionarily conserved from bat CoV-HKU4 to human endemic/emergent strains. Conserved dynamics regions of ACE2 involve both the N-terminal helices, as well as a region of more transient dynamics encompassing residues K353, Q325 and a novel motif AAQPFLL 386-92 that appears to coordinate their dynamic interactions with the viral RBD at N501. We also demonstrate that the functional evolution of Betacoronavirus zoonotic spillovers involving ACE2 interaction dynamics are likely pre-adapted from two precise and stable binding sites involving the viral bat progenitor strain's interaction with CD26 at SAMLI 291-5 and SS 333-334. Our analyses further indicate that the human endemic strains hCoV-HKU1 and hCoV-OC43 have evolved more stable N-terminal helix interactions through enhancement of an interfacing loop region on the viral RBD, whereas the highly transmissible SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1) have evolved more stable viral binding via more focused interactions between the viral N501 and ACE2 K353 alone.Communicated by Ramaswamy H. Sarma.

ZOVER: the database of zoonotic and vector-borne viruses.

Emerging infectious diseases significantly threaten global public health and socioeconomic security. The majority of emerging infectious disease outbreaks are caused by zoonotic/vector-borne viruses. Bats and rodents are the two most important reservoir hosts of many zoonotic viruses that can cross species barriers to infect humans, whereas mosquitos and ticks are well-established major vectors of many arboviral diseases. Moreover, some emerging zoonotic diseases require a vector to spread or are intrinsically vector-borne and zoonotically transmitted. In this study, we present a newly upgraded database of zoonotic and vector-borne viruses designated ZOVER (http://www.mgc.ac.cn/ZOVER). It incorporates two previously released databases, DBatVir and DRodVir, for bat- and rodent-associated viruses, respectively, and further collects up-to-date knowledge on mosquito- and tick-associated viruses to establish a comprehensive online resource for zoonotic and vector-borne viruses. Additionally, it integrates a set of online visualization tools for convenient comparative analyses to facilitate the discovery of potential patterns of virome diversity and ecological characteristics between/within different viral hosts/vectors. The ZOVER database will be a valuable resource for virologists, zoologists and epidemiologists to better understand the diversity and dynamics of zoonotic and vector-borne viruses and conduct effective surveillance to monitor potential interspecies spillover for efficient prevention and control of future emerging zoonotic diseases.

Seasonal shedding patterns of diverse henipavirus-related paramyxoviruses in Egyptian rousette bats.

Bat-borne viruses in the Henipavirus genus have been associated with zoonotic diseases of high morbidity and mortality in Asia and Australia. In Africa, the Egyptian rousette bat species (Rousettus aegyptiacus) is an important viral host in which Henipavirus-related viral sequences have previously been identified. We expanded these findings by assessing the viral dynamics in a southern African bat population. A longitudinal study of henipavirus diversity and excretion dynamics identified 18 putative viral species circulating in a local population, three with differing seasonal dynamics, and the winter and spring periods posing a higher risk of virus spillover and transmission. The annual peaks in virus excretion are most likely driven by subadults and may be linked to the waning of maternal immunity and recolonization of the roost in early spring. These results provide insightful information into the bat-host relationship that can be extrapolated to other populations across Africa and be communicated to at-risk communities as a part of evidence-based public health education and prevention measures against pathogen spillover threats.

The burden of zoonoses in Paraguay: A systematic review.

INTRODUCTION: Underestimation of zoonoses is exacerbated in low and middle-income countries due mainly to inequalities with serious consequences in healthcare. This is difficult to gauge and reduce the impact of those diseases. Our study focuses on Paraguay, where the livestock industry is one of the major components of the country's economy. Therefore, the rationale of this study was to develop a case study in Paraguay to estimate the dual impact of zoonotic diseases on both the human health and animal health sector and thus determine the societal burden of such diseases. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a systemic review (including a meta-analysis) to assess the burden of zoonoses in Paraguay, including official reports and grey literature of disease incidence and prevalence. We estimated the Disability Adjusted Life Years (DALYs) and Zoonosis Disability Adjusted Life Years (zDALYs) to measure the difference between the current health status and the desired health situation of animals and the Paraguayan population based on 50 zoonotic diseases suggested by the WHO (World Health Organization), OIE (World Organization for Animal Health) and the National Health in Paraguay. The total DALYs represent 19,384 (95% CI: from 15,805 to 29,733), and zDALYs, 62,178 (95% CI: from 48,696 to 77,188). According to the results, the priority pathogens for DALYs are E. coli, Trypanosoma cruzi, Leishmania spp, and Toxoplasma gondii. When we include the additional animal health burden, the most important pathogens are Brucella spp, E. coli, Trypanosoma cruzi, and Fasciola hepatica for zDALYs. CONCLUSION/SIGNIFICANCE: This is the first study to integrate DALYs and zDALYs with important clues related to the health status of Paraguay. Through DALYs and zDALYs, our perspective becomes more complete because we consider not only human health but also animal health. This is important for setting priorities in disease control, especially in a society where livestock contribute significantly to the economy and to human well-being.

The science of the host-virus network.

Better methods to predict and prevent the emergence of zoonotic viruses could support future efforts to reduce the risk of epidemics. We propose a network science framework for understanding and predicting human and animal susceptibility to viral infections. Related approaches have so far helped to identify basic biological rules that govern cross-species transmission and structure the global virome. We highlight ways to make modelling both accurate and actionable, and discuss the barriers that prevent researchers from translating viral ecology into public health policies that could prevent future pandemics.

How an outbreak became a pandemic: a chronological analysis of crucial junctures and international obligations in the early months of the COVID-19 pandemic.

Understanding the spread of SARS-CoV-2, how and when evidence emerged, and the timing of local, national, regional, and global responses is essential to establish how an outbreak became a pandemic and to prepare for future health threats. With that aim, the Independent Panel for Pandemic Preparedness and Response has developed a chronology of events, actions, and recommendations, from December, 2019, when the first cases of COVID-19 were identified in China, to the end of March, 2020, by which time the outbreak had spread extensively worldwide and had been characterised as a pandemic. Datapoints are based on two literature reviews, WHO documents and correspondence, submissions to the Panel, and an expert verification process. The retrospective analysis of the chronology shows a dedicated initial response by WHO and some national governments, but also aspects of the response that could have been quicker, including outbreak notifications under the International Health Regulations (IHR), presumption and confirmation of human-to-human transmission of SARS-CoV-2, declaration of a Public Health Emergency of International Concern, and, most importantly, the public health response of many national governments. The chronology also shows that some countries, largely those with previous experience with similar outbreaks, reacted quickly, even ahead of WHO alerts, and were more successful in initially containing the virus. Mapping actions against IHR obligations, the chronology shows where efficiency and accountability could be improved at local, national, and international levels to more quickly alert and contain health threats in the future. In particular, these improvements include necessary reforms to international law and governance for pandemic preparedness and response, including the IHR and a potential framework convention on pandemic preparedness and response.

Porcine Endogenous Retroviruses and Xenotransplantation, 2021.

Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and some of them are able to infect human cells. Therefore, PERVs pose a risk for xenotransplantation, the transplantation of pig cells, tissues, or organ to humans in order to alleviate the shortage of human donor organs. Up to 2021, a huge body of knowledge about PERVs has been accumulated regarding their biology, including replication, recombination, origin, host range, and immunosuppressive properties. Until now, no PERV transmission has been observed in clinical trials transplanting pig islet cells into diabetic humans, in preclinical trials transplanting pig cells and organs into nonhuman primates with remarkable long survival times of the transplant, and in infection experiments with several animal species. Nevertheless, in order to prevent virus transmission to the recipient, numerous strategies have been developed, including selection of PERV-C-free animals, RNA interference, antiviral drugs, vaccination, and genome editing. Furthermore, at present there are no more experimental approaches to evaluate the full risk until we move to the clinic.

Identification of Hepatitis E Virus Genotypes 3 and 7 in Israel: A Public Health Concern?

BACKGROUND: Hepatitis E (HEV) is an emerging cause of viral hepatitis worldwide. Swine carrying hepatitis E genotype 3 (HEV-3) are responsible for the majority of chronic viral hepatitis cases in developed countries. Recently, genotype 7 (HEV-7), isolated from a dromedary camel in the United Arab Emirates, was also associated with chronic viral hepatitis in a transplant recipient. In Israel, chronic HEV infection has not yet been reported, although HEV seroprevalence in humans is ~10%. Camels and swine are >65% seropositive. Here we report on the isolation and characterization of HEV from local camels and swine. METHODS: Sera from camels (n = 142), feces from swine (n = 18) and blood from patients suspected of hepatitis E (n = 101) were collected during 2017-2020 and used to detect and characterize HEV sequences. RESULTS: HEV-3 isolated from local swine and the camel-derived HEV-7 sequence were highly similar to HEV-3f and HEV-7 sequences (88.2% and 86.4%, respectively) related to viral hepatitis. The deduced amino acid sequences of both isolates were also highly conserved (>98%). Two patients were HEV-RNA positive; acute HEV-1 infection could be confirmed in one of them. DISCUSSION: The absence of any reported HEV-3 and HEV-7 infection in humans remains puzzling, especially considering the reported seroprevalence rates, the similarity between HEV sequences related to chronic hepatitis and the HEV genotypes identified in swine and camels in Israel.

Gut microbiota of bats: pro-mutagenic properties and possible frontiers in preventing emerging disease.

Bats are potential natural reservoirs for emerging viruses, causing deadly human diseases, such as COVID-19, MERS, SARS, Nipah, Hendra, and Ebola infections. The fundamental mechanisms by which bats are considered "living bioreactors" for emerging viruses are not fully understood. Some studies suggest that tolerance to viruses is linked to suppressing antiviral immune and inflammatory responses due to DNA damage by energy generated to fly. Our study reveals that bats' gut bacteria could also be involved in the host and its microbiota's DNA damage. We performed screening of lactic acid bacteria and bacilli isolated from bats' feces for mutagenic and oxidative activity by lux-biosensors. The pro-mutagenic activity was determined when expression of recA increased with the appearance of double-strand breaks in the cell DNA, while an increase of katG expression in the presence of hydroxyl radicals indicated antioxidant activity. We identified that most of the isolated bacteria have pro-mutagenic and antioxidant properties at the same time. This study reveals new insights into bat gut microbiota's potential involvement in antiviral response and opens new frontiers in preventing emerging diseases originating from bats.

Airborne Transmission of Avian Origin H9N2 Influenza A Viruses in Mammals.

Influenza A viruses (IAV) are widespread viruses affecting avian and mammalian species worldwide. IAVs from avian species can be transmitted to mammals including humans and, thus, they are of inherent pandemic concern. Most of the efforts to understand the pathogenicity and transmission of avian origin IAVs have been focused on H5 and H7 subtypes due to their highly pathogenic phenotype in poultry. However, IAV of the H9 subtype, which circulate endemically in poultry flocks in some regions of the world, have also been associated with cases of zoonotic infections. In this review, we discuss the mammalian transmission of H9N2 and the molecular factors that are thought relevant for this spillover, focusing on the HA segment. Additionally, we discuss factors that have been associated with the ability of these viruses to transmit through the respiratory route in mammalian species. The summarized information shows that minimal amino acid changes in the HA and/or the combination of H9N2 surface genes with internal genes of human influenza viruses are enough for the generation of H9N2 viruses with the ability to transmit via aerosol.