Based on recent multiregional epidemiological investigations of Monkeypox (MPX), on 24 July 2022, the World Health Organization declared it a global public health threat. Retrospectively MPX was an ignored zoonotic endemic infection to tropical rainforest regions of Western and Central African rural communities until a worldwide epidemic in May 2022 verified the potential threat of monkeypox virus (MPXV) to be propagated across the contemporary world via transnational tourism and animal movements. During 2018–2022, different cases of MPX diagnosed in Nigerian travelers have been documented in Israel, the United Kingdom, Singapore, and the United States. More recently, on 27 September 2022, 66,000 MPX cases have been confirmed in more than 100 non-endemic countries, with fluctuating epidemiological footprinting from retrospective epidemics. Particular disease-associated risk factors fluctuate among different epidemics. The unpredicted appearance of MPX in non-endemic regions suggests some invisible transmission dynamic. Hence, broad-minded and vigilant epidemiological attention to the current MPX epidemic is mandatory. Therefore, this review was compiled to highlight the epidemiological dynamic, global host ranges, and associated risk factors of MPX, concentrating on its epidemic potential and global public health threat.

PPRV infection induces cellular autophagy; however, the intracellular responses and signaling mechanisms that occur upon PPRV infection are obscure, and whether innate immune responses are linked with autophagy to regulate viral replication is largely unknown. Here, we uncovered that the innate immune sensor MDA5 initiated the signaling cascade by upregulating STING, which is best known for its role in anti-DNA virus infection by inducing interferon expression.

The present cross-sectional survey was carried out to investigate the distribution and risk factors of FMD in Pakistan’s northern border regions. About 385 serum samples were compiled from small ruminants (239) and large ruminants (146) and tested using 3ABC-Mab-bELISA. An overall apparent seroprevalence of 67.0% was documented. The highest seroprevalence of 81.1% was reported in the Swat, followed by 76.6% in Mohmand, 72.7% in Gilgit, 65.6% in Shangla, 63.4% in Bajaur, 46.6% in Chitral and lowest 46.5% in Khyber region. Statistically significant variations in seroprevalence of 51.5%, 71.8%, 58.3%, and 74.4% were recorded in sheep, goats, cattle, and buffaloes, respectively. From the different risk factors investigated, age, sex, species of animal, seasons, flock/herd size, farming methods, outbreak location, and nomadic animal movement were found to be significantly associated (p < 0.05) with the seroprevalence of FMD. It was concluded that proper epidemiological study, risk-based FMD surveillance in small ruminants, vaccination strategy, control measures for transboundary animal movement, collaborations, and awareness programs need to be practiced in the study regions to investigate the newly circulating virus strains in large and small ruminants and associated factors for the wide seroprevalence to plan proper control policies to bound the consequence of FMD in the region.

Seneca Valley Virus (SVV), a member of the Picornaviridae family, is an emerging porcine virus that can cause vesicular disease in pigs. However, the immune evasion mechanism of SVV remains unclear, as does its interaction with other pathways. STING (Stimulator of interferon genes) is typically recognized as a critical factor in innate immune responses to DNA virus infection, but its role during SVV infection remains poorly understood. In the present study, we observed that STING was degraded in SVV-infected PK-15 cells, and SVV replication in the cells was affected when STING was knockdown or overexpressed. The STING degradation observed was blocked when the SVV-induced autophagy was inhibited by using autophagy inhibitors (Chloroquine, Bafilomycin A1) or knockdown of autophagy related gene 5 (ATG5), suggesting that SVV-induced autophagy is responsible for STING degradation. Furthermore, the STING degradation was inhibited when reticulophagy regulator 1 (FAM134B), a reticulophagy related receptor, was knocked down, indicating that SVV infection induces STING degradation via reticulophagy. Further study showed that in eukaryotic translation initiation factor 2 alpha kinase 3 (PERK)/activating transcription factor 6 (ATF6) deficient cells, SVV infection failed to induce reticulophagy-medaited STING degradation, indicating that SVV infection caused STING degradation via PERK/ATF6-mediated reticulophagy. Notably, blocking reticulophagy effectively hindered SVV replication. Overall, our study suggested that SVV infection resulted in STING degradation via PERK and ATF6-mediated reticulophagy, which may be an immune escape strategy of SVV. This finding improves the understanding of the intricate interplay between viruses and their hosts and provides a novel strategy for the development of novel antiviral drugs.

Background: Canine distemper virus (CDV) is one of the most contagious and lethal viruses known to the Canidae, with a very broad and expanding host range. Autophagy serves as a fundamental stabilizing response against pathogens, but some viruses have been able to evade or exploit it for their replication. However, the effect of autophagy mechanisms on CDV infection is still unclear. Results: In the present study, autophagy was induced in CDV-infected Vero cells as demonstrated by elevated LC3-II levels and aggregation of green fluorescent protein (GFP)-LC3 spots. Furthermore, CDV promoted the complete autophagic process, which could be determined by the degradation of p62, co-localization of LC3 with lysosomes, GFP degradation, and accumulation of LC3-II and p62 due to the lysosomal protease inhibitor E64d. In addition, the use of Rapamycin to promote autophagy promoted CDV replication, and the inhibition of autophagy by Wortmannin, Chloroquine and siRNA-ATG5 inhibited CDV replication, revealing that CDV-induced autophagy facilitated virus replication. We also found that UV-inactivated CDV still induced autophagy, and that nucleocapsid (N) protein was able to induce complete autophagy in an mTOR-dependent manner. Conclusions: This study for the first time revealed that CDV N protein induced complete autophagy to facilitate viral replication.

Foot-and-mouth disease (FMD) is characterized by a pronounced lymphopenia that is associated with immune suppression. However, the mechanisms leading to lymphopenia remain unclear. In this study, the number of total CD4⁺, CD8⁺ T cells, B cells, and NK cells in the peripheral blood were dramatically reduced in C57BL/6 mice infected with foot-and-mouth disease virus (FMDV) serotype O, and it was noted that mice with severe clinical symptoms had expressively lower lymphocyte counts than mice with mild or without clinical symptoms, indicating that lymphopenia was associated with disease severity. A further analysis revealed that lymphocyte apoptosis and trafficking occurred after FMDV infection. In addition, coinhibitory molecules were upregulated in the expression of CD4⁺ and CD8⁺ T cells from FMDV-infected mice, including CTLA-4, LAG-3, 2B4, and TIGIT. Interestingly, the elevated IL-10 in the serum was correlated with the appearance of lymphopenia during FMDV infection but not IL-6, IL-2, IL-17, IL-18, IL-1β, TNF-α, IFN-α/β, TGF-β, and CXCL1. Knocking out IL-10 (IL-10^-/-) mice or blocking IL-10/IL-10R signaling in vivo was able to prevent lymphopenia via downregulating apoptosis, trafficking, and the coinhibitory expression of lymphocytes in the peripheral blood, which contribute to enhance the survival of mice infected with FMDV. Our findings support that blocking IL-10/IL-10R signaling may represent a novel therapeutic approach for FMD.