Airborne transmission of human-isolated avian H3N8 influenza virus between ferrets.

H3N8 avian influenza viruses (AIVs) in China caused two confirmed human infections in 2022, followed by a fatal case reported in 2023. H3N8 viruses are widespread in chicken flocks; however, the zoonotic features of H3N8 viruses are poorly understood. Here, we demonstrate that H3N8 viruses were able to infect and replicate efficiently in organotypic normal human bronchial epithelial (NHBE) cells and lung epithelial (Calu-3) cells. Human isolates of H3N8 virus were more virulent and caused severe pathology in mice and ferrets, relative to chicken isolates. Importantly, H3N8 virus isolated from a patient with severe pneumonia was transmissible between ferrets through respiratory droplets; it had acquired human-receptor-binding preference and amino acid substitution PB2-E627K necessary for airborne transmission. Human populations, even when vaccinated against human H3N2 virus, appear immunologically naive to emerging mammalian-adapted H3N8 AIVs and could be vulnerable to infection at epidemic or pandemic proportion.

Primate hemorrhagic fever-causing arteriviruses are poised for spillover to humans.

Simian arteriviruses are endemic in some African primates and can cause fatal hemorrhagic fevers when they cross into primate hosts of new species. We find that CD163 acts as an intracellular receptor for simian hemorrhagic fever virus (SHFV; a simian arterivirus), a rare mode of virus entry that is shared with other hemorrhagic fever-causing viruses (e.g., Ebola and Lassa viruses). Further, SHFV enters and replicates in human monocytes, indicating full functionality of all of the human cellular proteins required for viral replication. Thus, simian arteriviruses in nature may not require major adaptations to the human host. Given that at least three distinct simian arteriviruses have caused fatal infections in captive macaques after host-switching, and that humans are immunologically naive to this family of viruses, development of serology tests for human surveillance should be a priority.

The origins of SARS-CoV-2: A critical review.

Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a "laboratory escape" scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.

Emerging Pandemic Diseases: How We Got to COVID-19.

Infectious diseases prevalent in humans and animals are caused by pathogens that once emerged from other animal hosts. In addition to these established infections, new infectious diseases periodically emerge. In extreme cases they may cause pandemics such as COVID-19; in other cases, dead-end infections or smaller epidemics result. Established diseases may also re-emerge, for example by extending geographically or by becoming more transmissible or more pathogenic. Disease emergence reflects dynamic balances and imbalances, within complex globally distributed ecosystems comprising humans, animals, pathogens, and the environment. Understanding these variables is a necessary step in controlling future devastating disease emergences.

The Brucella Cell Envelope.

The cell envelope is a multilayered structure that insulates the interior of bacterial cells from an often chaotic outside world. Common features define the envelope across the bacterial kingdom, but the molecular mechanisms by which cells build and regulate this critical barrier are diverse and reflect the evolutionary histories of bacterial lineages. Intracellular pathogens of the genus Brucella exhibit marked differences in cell envelope structure, regulation, and biogenesis when compared to more commonly studied gram-negative bacteria and therefore provide an excellent comparative model for study of the gram-negative envelope. We review distinct features of the Brucella envelope, highlighting a conserved regulatory system that links cell cycle progression to envelope biogenesis and cell division. We further discuss recently discovered structural features of the Brucella envelope that ensure envelope integrity and that facilitate cell survival in the face of host immune stressors.

Evidence of zoonotic pathogens through biophysically induced genomic variance.

Zoonoses are infectious agents that are transmissible between animals and humans. Up to 60% of known infectious diseases and 75% of emergent diseases are zoonotic. Genomic variation between homeostatic populations provides a novel window into the effect of environmental pathogens on allelic distributions within the populations. Genodynamics is a biophysical approach utilizing developed metrics on biallelic single-nucleotide polymorphisms (SNPs) that can be used to quantify the adaptive influences due to pathogens. A genomic free energy that is minimized when overall population health is optimized describes the influence of environmental agents upon genomic variation. A double-blind exploration of over 100 thousand SNPs searching for smooth functional dependencies upon four zoonotic pathogens carried by four possible hosts amidst populations that live in their ancestral environments has been conducted. Exemplars that infectious agents can have significant adaptive influence on human populations are presented. One discussed SNP is likely associated with both adaptive and innate immune regulation. The adaptive response of another SNP suggests an intriguing connection between zoonoses and human cancers. The adaptive forces of the presented pathogens upon the human genome have been quantified.

Mpox: The Reemergence of an Old Disease and Inequities.

Mpox, previously known as monkeypox, is caused by an Orthopoxvirus related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to central and west Africa. Since May 2022, more than 86,000 cases of mpox from 110 countries have been identified across the world, predominantly in men who have sex with men, most often acquired through close physical contact or during sexual activity. The classical clinical presentation of mpox is a prodrome including fever, lethargy, and lymphadenopathy followed by a characteristic vesiculopustular rash. The recent 2022 outbreak included novel presentations of mpox with a predominance of anogenital lesions, mucosal lesions, and other features such as anorectal pain, proctitis, oropharyngeal lesions, tonsillitis, and multiphasic skin lesions. We describe the demographics and clinical spectrum of classical and novel mpox, outlining the potential complications and management.

The harms of promoting the lab leak hypothesis for SARS-CoV-2 origins without evidence.

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.

Transmission dynamics, complications and mitigation strategies of the current mpox outbreak: A comprehensive review with bibliometric study.

As the mankind counters the ongoing COVID-19 pandemic by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), it simultaneously witnesses the emergence of mpox virus (MPXV) that signals at global spread and could potentially lead to another pandemic. Although MPXV has existed for more than 50 years now with most of the human cases being reported from the endemic West and Central African regions, the disease is recently being reported in non-endemic regions too that affect more than 50 countries. Controlling the spread of MPXV is important due to its potential danger of a global spread, causing severe morbidity and mortality. The article highlights the transmission dynamics, zoonosis potential, complication and mitigation strategies for MPXV infection, and concludes with suggested 'one health' approach for better management, control and prevention. Bibliometric analyses of the data extend the understanding and provide leads on the research trends, the global spread, and the need to revamp the critical research and healthcare interventions. Globally published mpox-related literature does not align well with endemic areas/regions of occurrence which should ideally have been the scenario. Such demographic and geographic gaps between the location of the research work and the endemic epicentres of the disease need to be bridged for greater and effective translation of the research outputs to pubic healthcare systems, it is suggested.

Enveloped viruses show increased propensity to cross-species transmission and zoonosis.

The transmission of viruses between different host species is a major source of emerging diseases and is of particular concern in the case of zoonotic transmission from mammals to humans. Several zoonosis risk factors have been identified, but it is currently unclear which viral traits primarily determine this process as previous work has focused on a few hundred viruses that are not representative of actual viral diversity. Here, we investigate fundamental virological traits that influence cross-species transmissibility and zoonotic propensity by interrogating a database of over 12,000 mammalian virus-host associations. Our analysis reveals that enveloped viruses tend to infect more host species and are more likely to be zoonotic than nonenveloped viruses, while other viral traits such as genome composition, structure, size, or the viral replication compartment play a less obvious role. This contrasts with the previous notion that viral envelopes did not significantly impact or even reduce zoonotic risk and should help better prioritize outbreak prevention efforts. We suggest several mechanisms by which viral envelopes could promote cross-species transmissibility, including structural flexibility of receptor-binding proteins and evasion of viral entry barriers.

Clinical Manifestations of an Outbreak of Monkeypox Virus in Captive Chimpanzees in Cameroon, 2016.

Monkeypox virus (MPXV) is a reemerging virus of global concern. An outbreak of clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, perilaryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees, with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures.

Potential for Person-to-Person Transmission of Henipaviruses: A Systematic Review of the Literature.

Nipah virus Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus Malaysia (NiVM), is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread. More than 600 human infections have been reported in the literature, but information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, and some evidence for NiVM. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVM, suggesting potential for transmission. As the group of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed.

Long-term Elevation of Complement Factors in Cerebrospinal Fluid of Patients With Borna Disease Virus 1 Encephalitis.

BACKGROUND: Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and in viral infections of the central nervous system is increasing and specific inhibitors are available as therapeutic options. METHODS: In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to noninflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using postmortem brain tissue samples. RESULTS: We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent, and C3 complement deposits were detected in postmortem brain sections. Intrathecal complement levels were negatively correlated with survival. CONCLUSIONS: Further investigations are warranted to clarify whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis.

Human infection with IsrRAPXV, a novel zoonotic bat-derived poxvirus.

BACKGROUND: Bats are recognized as the natural reservoir of several zoonotic viruses that pose a threat to public health worldwide. In our recent reports we describe the identification of a novel poxvirus, IsrRAPXV, in Egyptian fruit bats. This poxvirus is associated with high morbidity and mortality in bats. METHODS: Herein, we describe the identification of poxvirus in a female patient hospitalized with systemic symptoms and severe painful skin lesions on her hands. We performed qPCR, whole genome sequencing and phylogenetic analysis to identify and characterize this poxvirus as the etiologic agent. RESULTS: The patient interacted with wounded and sick bats as a volunteer in a bat shelter run by the Israel bat sanctuary organization. Samples collected from the patient's skin lesions were positive for the presence of IsrRAPXV by PCR. Additionally, phylogenetic analysis showed that this virus is identical to IsrRAPXV originally described by us as the causative agent of skin lesions in fruit bats. CONCLUSIONS: Our finding suggest that IsrRAPXV is zoonotic and therefore veterinarians and volunteers working in bats shelter should meticulously follow the guidelines of working with bats and use required personal protective equipment.

Lyme Disease Surveillance and Epidemiology in the United States: A Historical Perspective.

In the 40 years since Steere and colleagues first described Lyme disease, the illness has increased in incidence and distribution to become the most common vector-borne disease in the United States. Public health officials have developed, implemented, and revised surveillance systems to describe and monitor the condition. Much has been learned about the epidemiology of the illness, despite practical and logistical constraints that have encumbered the collection and interpretation of surveillance data. Future development of automated data collection from electronic health records as a source of surveillance and clinical information will address practical challenges and help answer ongoing questions about complications and persistent symptoms. Robust surveillance will be essential to monitor the effectiveness and safety of future vaccines and other preventive measures.

A metagenomic investigation of the faecal RNA virome structure of asymptomatic chickens obtained from a commercial farm in Durban, KwaZulu-Natal province, South Africa.

BACKGROUND: Virome studies on birds, including chickens are relatively scarce, particularly from the African continent. Despite the continuous evolution of RNA viruses and severe losses recorded in poultry from seasonal viral outbreaks, the information on RNA virome composition is even scantier as a result of their highly unstable nature, genetic diversity, and difficulties associated with characterization. Also, information on factors that may modulate the occurrence of some viruses in birds is limited, particularly for domesticated birds. Viral metagenomics through advancements in sequencing technologies, has enabled the characterization of the entire virome of diverse host species using various samples. METHODS: The complex RNA viral constituents present in 27 faecal samples of asymptomatic chickens from a South African farm collected at 3-time points from two independent seasons were determined, and the impact of the chicken's age and collection season on viral abundance and diversity was further investigated. The study utilized the non-invasive faecal sampling method, mRNA viral targeted enrichment steps, a whole transcriptome amplification strategy, Illumina sequencing, and bioinformatics tools. RESULTS: The results obtained revealed a total of 48 viral species spanning across 11 orders, 15 families and 21 genera. Viral RNA families such as Coronaviridae, Picornaviridae, Reoviridae, Astroviridae, Caliciviridae, Picorbirnaviridae and Retroviridae were abundant, among which picornaviruses, demonstrated a 100% prevalence across the three age groups (2, 4 and 7 weeks) and two seasons (summer and winter) of the 27 faecal samples investigated. A further probe into the extent of variation between the different chicken groups investigated indicated that viral diversity and abundance were significantly influenced by age (P = 0.01099) and season (P = 0.00099) between chicken groups, while there was no effect on viral shedding within samples in a group (alpha diversity) for age (P = 0.146) and season (P = 0.242). CONCLUSION: The presence of an exceedingly varied chicken RNA virome, encompassing avian, mammalian, fungal, and dietary-associated viruses, underscores the complexities inherent in comprehending the causation, dynamics, and interspecies transmission of RNA viruses within the investigated chicken population. Hence, chickens, even in the absence of discernible symptoms, can harbour viruses that may exhibit opportunistic, commensal, or pathogenic characteristics.

Genetic Independence of Naturally Correlated Variation in Resistance to Endemic and Novel Pathogens.

The emergence of new diseases is an urgent concern, but hosts can also vary in resistance to pathogens that are novel to them, facilitating evolutionary rescue. However, little is known about the genetic source for polymorphic resistance to novel pathogens or its relationship to defences against endemic diseases. With anther-smut disease from wild plant populations, we used selection experiments and genetic analyses to show that resistances to novel and endemic pathogens are genetically independent, despite being positively correlated in nature. Moreover, novel-pathogen resistance presented a much simpler genetic basis and more rapid response to selection. We demonstrate that polymorphic resistance to a newly introduced disease is genetically determined and not an extension of defences against the related endemic pathogen, challenging the conventional view of nonhost resistance.

Microsporidia (Encephalitozoon cuniculi) in Patients with Degenerative Hip and Knee Disease, Czech Republic.

Total joint arthroplasty is a commonly used surgical procedure in orthopedics. Revision surgeries are required in >10% of patients mainly because of prosthetic joint infection caused by bacteria or aseptic implant loosening caused by chronic inflammation. Encephalitozoon cuniculi is a microsporidium, an obligate intracellular parasite, capable of exploiting migrating proinflammatory immune cells for dissemination within the host. We used molecular detection methods to evaluate the incidence of E. cuniculi among patients who had total hip or knee arthroplasty revision. Out of 49 patients, E. cuniculi genotypes I, II, or III were confirmed in joint samples from 3 men and 2 women who had implant loosening. Understanding the risks associated with the presence of microsporidia in periprosthetic joint infections is essential for proper management of arthroplasty. Furthermore, E. cuniculi should be considered a potential contributing cause of joint inflammation and arthrosis.

Link between Monkeypox Virus Genomes from Museum Specimens and 1965 Zoo Outbreak.

We used pathogen genomics to test orangutan specimens from a museum in Bonn, Germany, to identify the origin of the animals and the circumstances of their death. We found monkeypox virus genomes in the samples and determined that they represent cases from a 1965 outbreak at Rotterdam Zoo in Rotterdam, the Netherlands.

Variation in bacterial pathotype is consistent with the sit-and-wait hypothesis.

The sit-and-wait hypothesis predicts that bacteria can become more virulent when they survive and transmit outside of their hosts due to circumventing the costs of host mortality. While this hypothesis is largely supported theoretically and through comparative analysis, experimental validation is limited. Here we test this hypothesis in Streptococcus suis, an opportunistic zoonotic pig pathogen, where a pathogenic ecotype proliferated during the change to intensive pig farming that amplifies opportunities for fomite transmission. We show in an in vitro environmental survival experiment that pathogenic ecotypes survive for longer than commensal ecotypes, despite similar rates of decline. The presence of a polysaccharide capsule has no consistent effect on survival. Our findings suggest that extended survival in the food chain may augment the zoonotic capability of S. suis. Moreover, eliminating the long-term environmental survival of bacteria could be a strategy that will both enhance infection control and curtail the evolution of virulence.