Journal of General Virology: Most Read This Month http://www.microbiologyresearch.org/content/journal/jgv?TRACK=RSS Please follow the links to view the content. Oropouche Virus: An Emerging Orthobunyavirus http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002027?TRACK=RSS On 2 February 2024, the Pan American Health Organization/World Health Organization issued an epidemiological alert on rising Oropouche virus (OROV) infections in South America. By 3 August 2024, this alert level had escalated from medium to high. OROV has been a public health concern in Central and South America since its emergence in Brazil in the 1960s. However, the 2024 outbreak marks a turning point, with the sustained transmission in non-endemic regions of Brazil, local transmission in Cuba, two fatalities and several cases of vertical transmission. As of the end of August 2024, 9852 OROV cases have been confirmed. The 2024 OROV outbreak underscores critical gaps in our understanding of OROV pathogenesis and highlights the urgent need for antivirals and vaccines. This review aims to provide a concise overview of OROV, a neglected orthobunyavirus. Natasha L. Tilston-Lunel 2024-10-01T09:49:05Z Resolving the differential distribution of structural proteins in baculovirus using single-molecule localization microscopy http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002054?TRACK=RSS Baculovirus is one of the most complex viruses found in nature. Proteomic analysis of budded viruses (BVs) indicates that they are formed by at least 50 different structural proteins. The function of most of these structural proteins and their specific localization in individual virions remain unknown. In the present study, we have conducted single-molecule localization microscopy analysis of the spatial distribution of the nucleocapsid protein P24 and the envelope proteins GP64 and E25. Our results show that P24 and GP64 are polarized to one end of the baculovirus, while E25 distributes more homogenously along the viral envelope. This is the first study using optical microscopy to demonstrate the polarized distribution of structural proteins in individual baculoviruses. Daniel Martínez-Flores, Aaron Pavel Rodríguez-Hernández, Alicia Sampieri, Adolfo Cruz-Reséndiz, Ileana Tobías-Juárez, Reyna Lara-Martínez, Luis F Jiménez-García and Luis Vaca 2024-12-02T14:38:59Z ICTV Virus Taxonomy Profile: Coronaviridae 2023 http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001843?TRACK=RSS The family Coronaviridae includes viruses with positive-sense RNA genomes of 22–36 kb that are expressed through a nested set of 3′ co-terminal subgenomic mRNAs. Members of the subfamily Orthocoronavirinae are characterized by 80–160 nm diameter, enveloped virions with spike projections. The orthocoronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome-related coronavirus are extremely pathogenic for humans and in the last two decades have been responsible for the SARS and MERS epidemics. Another orthocoronavirus, severe acute respiratory syndrome coronavirus 2, was responsible for the recent global COVID-19 pandemic. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Coronaviridae which is available at www.ictv.global/report/coronaviridae. Patrick C. Y. Woo, Raoul J. de Groot, Bart Haagmans, Susanna K. P. Lau, Benjamin W. Neuman, Stanley Perlman, Isabel Sola, Lia van der Hoek, Antonio C. P. Wong and Shiou-Hwei Yeh 2023-04-25T15:56:00Z Emergence of highly pathogenic avian influenza viruses H5N1 and H5N5 in white-tailed eagles, 2021–2023 http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002035?TRACK=RSS Highly pathogenic avian influenza (HPAI) poses a substantial threat to several raptors. Between 2021 and 2023, HPAI viruses (HPAIVs) of the Goose/Guangdong lineage H5 clade 2.3.4.4b became widespread in wild birds in Norway, and H5N1 and H5N5 viruses were detected in 31 white-tailed eagles (Haliaeetus albicilla, WTEs). Post-mortem examinations of four WTEs revealed no macroscopic pathological findings. Microscopic examinations showed the presence of myocardial and splenic necroses and a few lesions in the brain. In situ hybridization revealed the presence of the virus in several organs, suggesting a multisystemic infection. The detection of HPAIV H5N5 in a WTE in February 2022 marked the first recorded occurrence of this subtype in Norway. Since then, the virus has persisted, sporadically being detected in WTEs and other wild bird species. Phylogenetic analyses reveal that at least two distinct incursions of HPAIV H5N1 Eurasian (EA) genotype C affected WTEs, likely introduced by migratory birds from Eurasia and seabirds entering from Western and Central Europe. Some WTE isolates from 2021 to 2022 clustered with those from Canada and Ireland, aligning with the transatlantic spread of H5N1. Others were related to the 2021 mass mortality of great skuas in the UK or outbreaks in seabird populations, including gannets, gulls and terns, during 2022 in the North Sea region. This suggests that the WTEs were likely preying on the affected birds. Our study highlights that WTEs can act as sentinels for some HPAIV strains, but the absence of several known circulating genotypes in WTEs suggests varying pathogenic effects on this species. Cathrine Arnason Bøe, Eve Marie Louise Zeyl Fiskebeck, Malin Rokseth Reiten, Johan Åkerstedt, Maryam Saghafian, Ragnhild Tønnessen, Britt Gjerset, Kjersti Sturød, Torfinn Moldal, Grim Rømo, Morten Helberg, Duncan Halley, Lars-Erik Lundblad Rondestveit, Knut Madslien and Silje Granstad 2024-11-01T16:04:00Z Comparison of different T cell assays for the retrospective determination of SARS-CoV-2 infection http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002055?TRACK=RSS It is important to be able to retrospectively determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections with high accuracy, both for post-coronavirus disease 2019 (COVID-19) epidemiological studies, and to distinguish between Long COVID and other multi-syndromic diseases that have overlapping symptoms. Although serum antibody levels can be measured to retrospectively diagnose SARS-CoV-2 infections, peptide stimulation of memory T cell responses is a more sensitive approach. This is because robust memory T cells are generated after SARS-CoV-2 infection and persist even after antibodies wane below detectability thresholds. In this study, we compare T cell responses using FluoroSpot-based methods and overnight stimulation of whole blood with SARS-CoV-2 peptides followed by an ELISA. Both approaches have comparable sensitivity and specificity but require different equipment and samples to be used. Furthermore, the elimination of peptides that cross-react with other coronaviruses increases the assay specificity but trades off some sensitivity. Finally, this approach can be used on archival, cryopreserved PBMCs. This work shows comparative advantages for several methods to measure SARS-CoV-2 T cell responses that could be utilized by any laboratory studying the effects of the coronavirus disease 2019 pandemic. Benjamin Krishna, Marina Metaxaki, Marianne Perera, Mark Wills and Nyarie Sithole 2024-12-20T09:01:31Z U-73122, a phospholipase C inhibitor, impairs lymphocytic choriomeningitis virus virion infectivity http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002060?TRACK=RSS Lassa virus (LASV) is an Old World (OW) mammarenavirus that causes Lassa fever, a life-threatening acute febrile disease endemic in West Africa. Lymphocytic choriomeningitis virus (LCMV) is a worldwide-distributed, prototypic OW mammarenavirus of clinical significance that has been largely neglected as a human pathogen. No licensed OW mammarenavirus vaccines are available, and the current therapeutic option is limited to the off-label use of ribavirin, which offers only partial efficacy. This situation underscores the urgent need to develop novel antivirals against human pathogenic mammarenaviruses. Previously, we showed that afatinib, a pan-ErbB tyrosine kinase inhibitor, inhibited multiple steps of the life cycles of OW LASV and LCMV, as well as the New World Junín virus vaccine strain Candid#1. In the present study, we investigated the inhibitory effect of U-73122, a phospholipase C inhibitor that acts downstream of ErbB signalling, on LCMV multiplication. U-73122 inhibited WT recombinant (r) LCMV multiplication in cultured cells. Preincubation of cell-free LCMV virions with U-73122 resulted in impaired virion infectivity. U-73122 also inhibited the infection of rLCMVs expressing heterologous viral glycoproteins, including the vesicular stomatitis Indiana virus (VSIV) glycoprotein, whereas WT VSIV infection was not affected by U-73122 treatment. Our results show the novel bioactivity of U-73122 as an LCMV inhibitor and indicate the presence of a virion-associated molecule that is necessary for virion infectivity and can be exploited as a potential antiviral drug target against human pathogenic mammarenavirus infections. Keita Mizuma, Mei Hashizume, Shuzo Urata, Keiko Shindo, Ayako Takashima, Satoshi Mizuta and Masaharu Iwasaki 2024-12-17T15:57:23Z Therapeutic efficacy of JNJ-49214698, an RSV fusion inhibitor, in RSV-infected neonatal lambs http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002056?TRACK=RSS Respiratory syncytial virus (RSV) is a leading cause of respiratory infection, hospitalization and death in infants worldwide. No fully effective RSV therapy using direct antivirals is marketed. Since clinical efficacy data from naturally infected patients for such antivirals are not available yet, animal studies are indispensable to predict therapeutic intervention. Here, we report the impact of an RSV fusion inhibitor, JNJ-49214698, on severe RSV-associated acute lower respiratory tract infection (ALRTI) in neonatal lambs. Randomized animals were treated once daily with 25 mg/kg JNJ-49214698, starting either before RSV infection, 1 day post-infection or as late as peak lung viral load on Day 3 post-infection. Treatment efficacy was assessed by scoring clinical signs of illness, development of RSV-induced gross and microscopic lung lesions and measuring virus titres in the lungs. Treatment with JNJ-49214698 was very effective in all treatment groups. Even in animals for which treatment was delayed until peak viral load was reached, a reduced amount and severity of gross and microscopic lesions, as well as RSV titres and RNA levels, were found. These results strongly suggest that treatment with small-molecule fusion inhibitors is an effective strategy to treat patients who are diagnosed with an RSV-induced ALRTI. Sarhad Alnajjar, Alejandro Larios-Mora, Albert Van-Geelen, Jack Gallup, Anil Koul, Peter Rigaux, Dirk Roymans and Mark Ackermann 2024-12-11T16:30:15Z African lineage 1a West Nile virus isolated from crocodiles exhibits low neuroinvasiveness in mice http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002051?TRACK=RSS West Nile virus (WNV) is a mosquito-borne flavivirus that causes encephalitis in humans and infects crocodiles, resulting in rashes and neurological signs. In Zambia, two distinct lineages of WNV have been detected in neighbouring areas: lineage 2 in mosquitoes and lineage 1a in farmed crocodiles. Considering the risk of direct or vector-mediated WNV transmission from crocodiles to mammals, it is necessary to elucidate the pathogenicity of WNV strains derived from crocodiles. In this study, WNV was successfully isolated from naturally infected farmed crocodiles (Croc110/2019/1/ZM, Croc110). We then investigated its proliferation and pathogenicity in mice in comparison with a WNV isolate from mosquitoes in Zambia (Zmq16) and two reference strains, including one highly pathogenic (NY99) and one low pathogenic (Eg101) strain. Although viral proliferation in Vero and mammalian neuronal cells was comparable among the strains, Croc110 exhibited low cell-to-cell transmission efficiency. In vivo, more than 70% of mice (C57BL/6) intracerebrally inoculated with Croc110 displayed neurological signs, and Croc110-infected mice exhibited similarly high mortality rates as NY99- and Zmq16-infected mice. Meanwhile, comparable virus growth was observed among the strains in the brain. However, the virulence of Croc110 was significantly lower than that of Zmq16 and NY99 following intradermal (ID) and intraperitoneal inoculation. Consistently, Croc110 displayed lower growth than Zmq16 and NY99 in the brain and peripheral tissues after ID inoculation. Our study revealed that the crocodile-derived WNV strain is less neuroinvasive in mice, and it exhibits distinct pathogenicity from the highly pathogenic mosquito-derived WNV strain circulating in Zambia. Hiroko Kobayashi, Herman Chambaro, Koshiro Tabata, Takuma Ariizumi, Wallaya Phongphaew, Kunda Ndashe, Joseph Ndebe, Paul Fandamu, Shintaro Kobayashi, Naoto Ito, Michihito Sasaki, Bernard M. Hang’ombe, Edgar Simulundu, Yasuko Orba and Hirofumi Sawa 2024-11-26T15:11:55Z ICTV Virus Taxonomy Profile: Hepeviridae 2022 http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001778?TRACK=RSS The family Hepeviridae includes enterically transmitted small quasi-enveloped or non-enveloped positive-sense single-stranded RNA viruses infecting mammals and birds (subfamily Orthohepevirinae) or fish (Parahepevirinae). Hepatitis E virus (genus Paslahepevirus) is responsible for self-limiting acute hepatitis in humans; the infection may become chronic in immunocompromised individuals and extrahepatic manifestations have been described. Avian hepatitis E virus (genus Avihepevirus) causes hepatitis–splenomegaly syndrome in chickens. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hepeviridae, which is available at www.ictv.global/report/hepeviridae. Michael A. Purdy, Jan Felix Drexler, Xiang-Jin Meng, Heléne Norder, Hiroaki Okamoto, Wim H. M. Van der Poel, Gábor Reuter, William M. de Souza, Rainer G. Ulrich and Donald B. Smith 2022-09-28T15:56:00Z Challenges on the development of a dengue vaccine: a comprehensive review of the state of the art http://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001831?TRACK=RSS Dengue virus (DENV) is the mosquito-borne virus of greatest human health concern. There are four serotypes of DENV (1-4) that co-circulate in endemic areas. Each serotype of DENV is individually capable of causing the full spectrum of disease, ranging from self-resolving dengue fever to the more severe dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Based on data published by the CDC, one in four people who become infected with dengue will become ill. Of those that do develop symptomology, the symptoms can range from mild to severe. Symptoms can vary from rash, ocular aches and pains to more intense symptoms in the manifestation of severe dengue. Roughly, 1 in 20 people who become ill will develop severe dengue, which can result in shock, internal bleeding and death. There is currently no specific treatment for dengue and only one licensed vaccine (Dengvaxia) for children 9 through 16 years of age in just a few countries. Despite its licensure for clinical use, Dengvaxia has performed with low efficacy in children and dengue naïve individuals and critically has resulted in increased risk of developing severe dengue in young, vaccinated recipients. Currently, there are various novel strategies for the development of a dengue vaccine. In this review we have conducted a detailed overview of the DENV vaccine landscape, focusing on nine vaccines in the pipeline to provide a comprehensive overview of the most state-of-the-art developments in strategies for vaccines against DENV. Jessica Pintado Silva and Ana Fernandez-Sesma 2023-03-01T17:27:33Z