Explore the vast range of titles available.

Key Points Influenza pandemics are caused when influenza viruses that possess a viral surface protein — haemagglutinin (HA) — to which the majority of people lack immunity spreads from human to human within the population. There were four influenza pandemics in the 20th century: the Spanish influenza of 1918–1919, which was caused by an H1N1 virus and killed at least 40 million people; the 1957 Asian influenza, which was caused by an H2N2 virus; the 1968 Hong Kong influenza, which was caused by an H3N2 virus; and the 1977 Russian influenza, which was caused by an H1N1 virus. With the exception of the Russian pandemic strain, which was identical to H1N1 viruses that circulated in humans in the 1950s and is therefore suspected to have been reintroduced to the population from a freezer somewhere, all 20th century pandemics were characterized by the acquisition of HAs from avian viruses. Clues to the molecular changes that give rise to human pandemic strains are therefore being sought in the avian virus reservoir. Avian influenza viruses are classified into two main types, on the basis of virulence: highly pathogenic avian influenza (HPAI) viruses cause systemic lethal infection with high mortality, whereas low-pathogenic avian influenza (LPAI) viruses cause localized infections with much lower mortality. The viral HA has been identified as having a key role in this variable pathogenicity. A precursor HA molecule must undergo post-translational proteolytic cleavage. The HAs of LPAI viruses possess a single basic residue at the cleavage site and are usually cleaved by proteases found in only a limited number of organs, whereas the HAs of HPAI viruses possess a series of basic amino acids at the cleavage site, which are cleaved by proteases present in a range of different host cells. Can avian viruses be transmitted directly to humans? Until 1997, it was thought that the answer to this question was no, but epidemiological evidence from an outbreak of H5N1 influenza in Hong Kong in May 1997 suggested direct transmission of the virus from birds to humans, although serological evidence of human-to-human transmission was limited. A more extensive outbreak of H5N1 influenza in poultry in 2003–2004 in Asia also spread to humans and resulted in 53 deaths. From the limited pathological information available, it is possible that cytokine dysregulation might have contributed to the pathogenesis of H5N1 disease in humans. Other outbreaks in which avian viruses have been transmitted directly to humans include an H7N7 outbreak in the Netherlands and two separate H9N2 outbreaks in Hong Kong. Efforts are underway to try and identify the molecular features that are important for human infection, although it is expected that the growth and pathogenicity of influenza viruses is multifactorial. Some of the viral gene products and functions that have been implicated include the role of HA in receptor specificity, the role of a viral RNA polymerase protein (PB1) in viral replication and host cell tropism and the role of the viral non-structural protein in pathogenicity in humans. Whether H5N1 viruses will acquire the ability to spread rapidly through human populations remains uncertain. However, in the event that an avian virus acquires specificity for human cell receptors and the other necessary genetic changes for human-to-human transmission, the resultant pandemic will have a devastating global impact. Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and H7 subtypes) in poultry and in humans (through direct contact with infected birds) have had important economic repercussions and have raised concerns that a new influenza pandemic will occur in the near future. The eradication of pathogenic avian influenza viruses seems to be the most effective way to prevent influenza pandemics, although this strategy has not proven successful so far. Here, we review the molecular factors that contribute to the emergence of pandemic strains.

Epidemiology of bat Betacoronavirus, subgenus Sarbecovirus is largely unknown, especially outside China. We detected a sarbecovirus phylogenetically related to severe acute respiratory syndrome coronavirus 2 from Rhinolophus cornutus bats in Japan. The sarbecovirus' spike protein specifically recognizes angiotensin-converting enzyme 2 of R. cornutus, but not humans, as an entry receptor.

Influenza D virus (IDV) can potentially cause respiratory diseases in livestock. We isolated a new IDV strain from diseased cattle in Japan; this strain is phylogenetically and antigenically distinguished from the previously described IDVs.

Viral infections have a significant impact on wildlife health, population dynamics, and ecosystem stability. Studies of cetaceans—key species in marine ecosystems—are challenging for viral infection research, owing to difficulties in collecting conventional biological samples. In this study, unmanned aerial vehicles (UAVs) were used in 2024 to noninvasively sample exhaled breath condensates (blows) from five groups of humpback whales (Megaptera novaeangliae) along the coastline of an island in the Pacific Ocean south of Japan. Comprehensive virome analysis revealed viral sequences related to 39 known virus species across 18 families, including nine that infect mammals. Notably, partial sequences of the UL20 gene similar to an alphaherpesvirus previously identified in beluga whales were detected for the first time in the blows from these humpback whales. Our study demonstrates that UAV-based blow sampling is an effective tool for virological surveillance in cetaceans. Moreover, our findings aid in advancing our understanding of the diversity of viruses in marine mammals and supporting the development of noninvasive monitoring strategies that are critical for ensuring the conservation and health of these creatures.

Pandemic virus characterized Analysis of a series of clinical isolates of the swine-origin H1N1 influenza virus reveals that in mammalian models (mice, ferrets and macaques) the current pandemic virus is associated with more severe disease than a seasonal H1N1 strain. The viruses can also infect pigs but do not cause clinical signs. All antivirus drugs tested, including Tamiflu, were effective in cell culture against the new virus, lending support to the use of these compounds as a first line of defence against the pandemic. On 11 June 2009 the World Health Organization declared that the infections caused by a new strain of influenza A virus closely related to swine viruses had reached pandemic levels. Here, one of the first US isolates of the new swine-origin H1N1 influenza virus (S-OIV) is characterized, as well as several other S-OIV isolates, both in vitro and in vivo . Influenza A viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On 11 June 2009 the World Health Organization declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses 1 . Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; hereafter referred to as CA04), as well as several other S-OIV isolates, in vitro and in vivo . In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen-free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting that these compounds could function as a first line of defence against the recently declared S-OIV pandemic.

Although a canine adenovirus (CAdV)-based oncolytic virus (OV) candidate targeting canine tumors has been reported, its oncolytic effect could be attenuated by CAdV vaccine-induced neutralizing antibodies in dog patients. To circumvent this issue, we focused on the bat adenovirus (BtAdV) strain, which was previously isolated from healthy microbats. We previously showed that this virus replicated efficiently in canine cell lines and did not serologically cross-react with CAdVs, suggesting that it may offer the possibility of an OV candidate for canine tumors. Here, we tested the growth properties and cytotoxicity of the BtAdV Mm32 strain in a panel of canine tumor cells and found that its characteristics were equivalent to those of CAdVs. To produce an Mm32 construct with enhanced tumor specificity, we established a novel reverse genetics system for BtAdV based on bacterial artificial chromosomes, and generated a recombinant virus, Mm32-E1Ap + cTERTp, by inserting a tumor-specific canine telomerase reverse transcriptase promoter into its E1A regulatory region. The growth and cytotoxicity of this recombinant were superior to those of wild-type Mm32 in canine tumor cells, unlike in normal canine cells. These data suggest that Mm32-E1Ap + cTERTp could be a promising OV for alternative canine cancer therapies.

Surveillance of bat betacoronaviruses is crucial for understanding their spillover potential. We isolated bat sarbecoviruses from Rhinolophus cornutus bats in multiple locations in Japan. These viruses grew efficiently in cells expressing R. cornutus angiotensin converting enzyme-2, but not in cells expressing human angiotensin converting enzyme-2, suggesting a narrow host range.

Bovine viral diarrhea virus (BVDV) is an important pathogen in cattle that causes economic losses in livestock industries. Autophagy is an essential cell system for the maintenance of homeostasis and is induced by various triggers, including infection by viruses. BVDV infection leads to autophagy in order to enhance its replication in cells. In this study, we investigated the effect of BVDV non-structural proteins on the induction of autophagosomes. We found that NS4B alone could induce autophagosomes, suggesting a novel and important function of NS4B in BVDV replication.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.

Influenza D virus (IDV) is a causative agent of the bovine respiratory disease complex (BRDC), which is the most common and costly disease affecting the cattle industry. For developing a candidate vaccine virus against IDV, we sought to produce a temperature-sensitive strain, similar to the live attenuated, cold-adapted vaccine strain available against the influenza A virus (IAV). To this end, we produced a recombinant IDV (designated rD/OK-AL) strain by introducing mutations responsible for the adaptation of the IAV vaccine strain to cold conditions and conferring sensitivity to high temperatures into PB2 and PB1 proteins using reverse genetics. The rD/OK-AL strain grew efficiently at 33 °C but did not grow at 37 °C in the cell culture, indicating its high-temperature sensitivity. In mice, rD/OK-AL was attenuated following intranasal inoculation. It mediated the production of high levels of antibodies against IDV in the serum. When the rD/OK-AL-inoculated mice were challenged with the wild-type virus, the virus was not detected in respiratory organs after the challenge, indicating complete protection against IDV. These results imply that the rD/OK-AL might be a potential candidate for the development of live attenuated vaccines for IDV that can be used to control BRDC.