Journal of General Virology最新文献

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.

Non-polio enteroviruses (NPEV) cause significant disease worldwide. Population-based sero-surveillance, by measuring antibodies against specific NPEV types, provides additional information on past circulation and the prediction for future upsurges. Virus neutralisation assays (VNA), the current method of choice for measuring NPEV type specific antibodies, are not entirely standardised. Via the European Non-Polio Enterovirus Network, we organised a VNA quality assessment in which twelve laboratories participated. We provided five echovirus (E) types (E1, E18, E30 G2, E30 G6 and E6) and intravenous immunoglobulins (IVIG) as a sample for the NPEV VNA quality assessment. Differences in VNA protocols and neutralising Ab (nAb) titres were found between the participating laboratories with geometric coefficients of variation ranging from 10.3-62.9 %. Mixed-effects regression analysis indicated a small but significant effect of type of cell line used. Harmonisation of cell line passage number, however, did not improve variation between laboratories. Calibration by making use of a reference sample, reduced variation between laboratories but differences in nAb titres remained higher than two log2 dilution steps. In conclusion, sero-surveillance data from different laboratories should be compared with caution and standardised protocols are needed.

Segmented RNA viruses are capable of exchanging genome segments via reassortment as a means of immune evasion and to maintain viral fitness. Reassortments of single-genome segments are common among group A rotaviruses. Multiple instances of co-reassortment of two genome segments, GS6(VP6) and GS10(NSP4), have been documented in surveillance. Specifically, a division between NSP4 genotypes has been observed in the NSP4 double-layered particle (DLP)-binding domain. A previously hypothesized mechanism for this co-reassortment has been suggested to be the interaction between VP6 and NSP4 during DLP transport from viroplasms for particle maturation. In this study, we used sequence analysis, RNA secondary structure prediction, molecular dynamics and reverse genetics to form a hypothesis regarding the role of the NSP4 DLP-binding domain. Sequence analysis showed that the polarity of NSP4 DLP-binding domain amino acids 169 and 174 is clearly divided between E1 and E2 NSP4 genotypes. Viruses with E1 NSP4s had 169A/I or 169S/T with 174S. E2 NSP4s had 169R/K and 174A. RNA secondary structure prediction showed that mutation in both 545 (aa169) and 561 (aa174) causes global structure remodelling. Molecular dynamics showed that the NSP4/VP6 interaction stability is increased by mutating both aa positions 169 and 174. Using reverse genetics, we showed that an R169I mutation alone does not prevent rescue. Conversely, 174A to 174S prevented rescue, and rescue could be returned by combining 174S with 169I. When compared to rSA11 NSP4-wt, both rSA11 NSP4-R169I and rSA11 NSP4-R169I/A174S had a negligible but significant reduction in titre at specific time points. This study suggests that amino acid 174 of NSP4 may be essential in maintaining the VP6/NSP4 interaction required for DLP transport. Our results suggest that maintenance of specific polarities of amino acids at positions 169 and 174 may be required for the fitness of rotavirus field strains.

Curly top disease caused by Beet curly top virus (BCTV) is a limiting factor for sugar beet production. The most economical and sustainable control of BCTV in sugar beet would be via the growth of resistant cultivars, although most commercial cultivars possess only low-to-moderate quantitative resistance. A double haploid line (KDH13) showed a high level of resistance to BCTV infection. However, the mechanism of resistance and response of this line to BCTV infection is unknown. Here, we tested the response of this line to both local and systemic BCTV infections. The virus replicated at a high level in locally infected tissue but lower than in susceptible KDH19 plants. Resistant KDH13 plants systemically infected with BCTV showed only mild enation without leaf curling after 30 days. In contrast, severe leaf curling appeared after 12 days in susceptible plants with higher virus accumulation. Transcriptome analysis of the BCTV-infected KDH13 plants at the early stage of symptom development showed only 132 genes that were exclusively deregulated compared to the regulation of a large number of genes (1018 genes) in KDH19 plants. Pathway enrichment analysis showed that differentially expressed genes were predominantly involved in hormone metabolism, DNA methylation, immune response, cell cycle, biotic stress and oxidative stress. The auxin level in both resistant and susceptible plants increased in response to BCTV infection. Remarkably, exogenous application of auxin caused leaf curling phenotype in the absence of the virus. This study demonstrates the response of resistant and susceptible plants to BCTV infection at both local and systemic infections and highlights the defence-related genes and metabolic pathways including auxin for their contribution towards BCTV symptom development and resistance in sugar beet.

Human noroviruses are the most common cause of viral gastroenteritis, resulting annually in 219 000 deaths and a societal cost of $60 billion, and no antivirals or vaccines are available. The minor capsid protein may play a significant role in the evolution of norovirus. GII.4 is the predominant genotype of norovirus, and its VP2 undergoes epochal co-evolution with the major capsid protein VP1. Since the sudden emergence of norovirus GII.2[P16] in 2016, it has consistently remained a significant epidemic strain in recent years. In the construction of phylogenetic trees, the phylogenetic trees of VP2 closely parallel those of VP1 due to the shared tree topology of both proteins. To investigate the interaction patterns between the major and minor capsid proteins of norovirus GII.2, we chose five representative strains of GII.2 norovirus and investigated their evolutionary patterns using a yeast two-hybrid experiment. Our study shows VP1-VP2 interaction in GII.2, with critical interaction sites at 167-178 and 184-186 in the highly variable region. In the intra-within GII.2, we observed no temporal co-evolution between VP1 and VP2 of GII.2. Notable distinctions were observed in the interaction intensity of VP2 among inter-genotype (P<0.05), highlighting the divergent evolutionary patterns of VP2 within different norovirus genotypes. In summary, the interactions between VP2 and VP1 of GII.2 norovirus exhibit out-of-sync evolutionary patterns. This study offered valuable insights for further understanding and completing the evolutionary mechanism of norovirus.

Fruit bats serve as an important reservoir for many zoonotic pathogens, including Nipah virus, Hendra virus, Marburg virus and Lyssavirus. To gain a deeper insight into the virological characteristics, pathogenicity and zoonotic potential of bat-borne viruses, recovery of infectious viruses from field samples is important. Here, we report the isolation and characterization of a mammalian orthoreovirus (MRV) from a large flying fox (Pteropus vampyrus) in Indonesia, which is the first detection of MRV in Southeast Asia. MRV was recovered from faecal samples of three different P. vampyrus in Central Java. Nucleotide sequence analysis revealed that the genome of the three MRV isolates shared more than 99% nucleotide sequence identity. We tentatively named one isolated strain as MRV12-52 for further analysis and characterization. Among 10 genome segments, MRV12-52 S1 and S4, which encode the cell-attachment protein and outer capsid protein, had 93.6 and 95.1% nucleotide sequence identities with known MRV strains, respectively. Meanwhile, the remaining genome segments of MRV12-52 were divergent with 72.9-80.7 % nucleotide sequence identities. Based on the nucleotide sequence of the S1 segment, MRV12-52 was grouped into serotype 2, and phylogenetic analysis demonstrated evidence of past reassortment events. In vitro characterization of MRV12-52 showed that the virus efficiently replicated in BHK-21, HEK293T and A549 cells. In addition, experimental infection of laboratory mice with MRV12-52 caused severe pneumonia with 75% mortality. This study highlights the presence of pathogenic MRV in Indonesia, which could serve as a potential animal and public health concern.

Rift Valley fever virus (Phlebovirus riftense, RVFV) poses significant economic challenges, particularly in African nations, causing substantial livestock losses and severe haemorrhagic disease in humans. In Europe, the risk of RVFV transmission is deemed moderate due to the presence of competent vectors like Culex pipiens and Aedes albopictus, along with susceptible animal vertebrate hosts across member states. This study investigates RVFV infection dynamics in European mosquito populations, aiming to enhance our understanding of their vectorial capacity and virus transmission, which can be useful for future investigations to improve RVFV surveillance, control programmes, and preventive treatments. Intrathoracic inoculation of European Cx. pipiens and Ae. albopictus with an RVFV virulent strain (RVF 56/74) enabled the assessment of virus tissue distribution and transmission. Immunohistochemistry analyses revealed widespread RVFV infection in all analysable anatomical structures at 5 and 14 days post-inoculation. Notably, the ganglionic nervous system exhibited the highest detection of RVFV in both species. Cx. pipiens showed more frequently infected structures than Ae. albopictus, particularly in reproductive structures. The identification of an RVFV-positive egg follicle in Cx. pipiens hints at potential vertical transmission. Saliva analysis indicated a higher transmission potential in Cx. pipiens (71.4%) compared to Ae. albopictus (4.3%) at the early time point. This study offers the first description and comparison of RVFV tissue distribution in Ae. albopictus and Cx. pipiens, shedding light on the susceptibility of their nervous systems, which may alter mosquito behaviour, which is critical for virus transmission. Overall, enhancing our knowledge of viral infection within mosquitoes holds promise for future vector biology research and innovative approaches to mitigate RVFV transmission.