Ecology and evolution of avian influenza viruses.

Four types of influenza virus have been identified in nature: influenza A, B, and C viruses are capable of infecting humans, and influenzas A and B cause annual epidemics (seasonal flu) in humans; however, influenza D is currently known to infect only pigs and cattle. The influenza A viruses (IAVs) are of greatest importance to humans, causing widespread significant morbidity and mortality, and have been responsible for at least five pandemics documented since the beginning of the 20th century (Table 1). The H1N1 and H3N2 IAVs continue to circulate in humans as seasonal influenza. In addition to humans, IAVs have a wide range of host animal species in nature, especially wild aquatic birds, the reservoir hosts of IAVs. The IAVs isolated from or adapted to an avian host are named avian influenza viruses (AIVs), and are of great concern owing to their involvement in the genesis of pandemic and outbreak strains. Moreover, the majority of AIVs persist in wild birds and domestic poultry, and novel variants continue to emerge in birds and other hosts, posing non-negligible threats to host ecology and public health.

Five-year longitudinal surveillance reveals the continual circulation of both alpha- and beta-coronaviruses in Plateau and Gansu pikas (Ochotona spp.) at Qinghai Lake, China.

AbstractThe discovery of alphacoronaviruses and betacoronaviruses in plateau pikas (Ochotona curzoniae) expanded the host range of mammalian coronavirus (CoV) to a new order - Lagomorpha. However, the diversity and evolutionary relationships of CoVs in these plateau-region-specific animal population remains uncertain. We conducted a five-year longitudinal surveillance of CoVs harbored by pikas around Qinghai Lake, China. CoVs were identified in 33 of 236 plateau pikas and 2 of 6 Gansu pikas (Ochotona cansus), with a total positivity rate of 14.5%, and exhibiting a wide spatiotemporal distribution across seven sampling sites and six time points. Through meta-transcriptomic sequencing and RT-PCR, we recovered 16 nearly-complete viral genome sequences. Phylogenetic analyses classified the viruses as variants of either pika alphacoronaviruses or betacoronaviruses endemic to plateau pikas from the Qinghai-Tibet Plateau region. Of particular note, the pika-associated betacoronaviruses may represent a novel subgenus within the genus Betacoronavirus. Tissue tropism, evaluated using quantitative real-time PCR, revealed the presence of CoV in the rectal and/or lung tissues, with the highest viral loads at 103.55 or 102.80 RNA copies/µL. Surface plasmon resonance (SPR) assays indicated that the newly identified betacoronavirus did not bind to human or pika Angiotensin-converting enzyme 2 (ACE2) or Dipeptidyl peptidase 4 (DPP4). The findings highlight the ongoing circulation and broadening host spectrum of CoVs among pikas, emphasizing the necessity for further investigation to evaluate their potential public health risks.

Serological Evidence of Bactrian Camel Infection with Tamdy Virus, Xinjiang, China.

Background: Tamdy Virus (TAMV) is a pathogenic nairovirus widely distributed in central Asia and northwestern China. However, the host range of TAMV remains unclear, which limits our understanding the transmission cycle and cross-species patterns of this virus. Materials and Methods: A total of 160 serum samples were collected from livestock animals of camels, cattle, and sheep in Xinjiang, China between 2018 and 2021. An indirect immunofluorescence assay for TAMV were developed in this study, and have been employed to test TAMV-specific antibodies in these serum samples. Results: TAMV IgG antibody was detectable in camel sera collected from Urumqi in 2018 (6/17, 35%) and also from the Alertai Region in 2021 (1/8, 12.5%). Conclusion: The serological results in this study provide the first evidence that TAMV is able to infect camels and that the pathogen is circulating in different regions of Xinjiang. These findings highlight the need to further increase clinical and epidemiological surveillance of TAMV in humans and livestock in northwestern China.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Fulminant myocarditis induced by SARS-CoV-2 infection without severe lung involvement: insights into COVID-19 pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often leads to pulmonary complications. Cardiovascular sequelae, including myocarditis and heart failure, have also been reported. Here, the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury, as determined by imaging examinations. Immunohistochemical staining reveals the viral antigen within cardiomyocytes, indicating that SARS-CoV-2 could directly infect the myocardium. The full viral genomes from respiratory, anal, and myocardial specimens are obtained via next-generation sequencing. Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples. In addition, unique mutations are found in the anal/myocardial strains compared to the respiratory strains, suggesting tissue-specific virus mutation and adaptation. These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues, independent of pulmonary injury, and point to different infection routes between the myocardium and respiratory tract, with myocardial infections potentially arising from intestinal infection. These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of the pathogenesis of COVID-19.

The extracellular cyclophilin A-integrin ß2 complex as a therapeutic target of viral pneumonia.

The acute respiratory virus infection can induce uncontrolled inflammatory responses, such as cytokine storm and viral pneumonia, which are the major causes of death in clinical cases. Cyclophilin A (CypA) is mainly distributed in the cytoplasm of resting cells and released into the extracellular space in response to inflammatory stimuli. Extracellular CypA (eCypA) is upregulated and promotes inflammatory response in severe COVID-19 patients. However, how eCypA promotes virus-induced inflammatory response remains elusive. Here, we observe that eCypA is induced by influenza A and B viruses and SARS-CoV-2 in cells, mice, or patients. Anti-CypA mAb reduces pro-inflammatory cytokines production, leukocytes infiltration, and lung injury in virus-infected mice. Mechanistically, eCypA binding to integrin ß2 triggers integrin activation, thereby facilitating leukocyte trafficking and cytokines production via the focal adhesion kinase (FAK)/GTPase and FAK/ERK/P65 pathways, respectively. These functions are suppressed by the anti-CypA mAb that specifically blocks eCypA-integrin ß2 interaction. Overall, our findings reveal that eCypA-integrin ß2 signaling mediates virus-induced inflammatory response, indicating that eCypA is a potential target for antibody therapy against viral pneumonia.