The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

Infectious threats to humans are continuously emerging. The 2022 worldwide monkeypox outbreak is the latest of these threats with the virus rapidly spreading to 106 countries by the end of September 2022. The burden of the ongoing monkeypox outbreak is manifested by 68,000 cumulative confirmed cases and 26 deaths. Although monkeypox is usually a self-limited disease, patients can suffer from extremely painful skin lesions and complications can occur with reported mortalities. The antigenic similarity between the smallpox virus (variola virus) and monkeypox virus can be utilized to prevent monkeypox using smallpox vaccines; treatment is also based on antivirals initially designed to treat smallpox. However, further studies are needed to fully decipher the immune response to monkeypox virus and the immune evasion mechanisms. In this review we provide an up-to-date discussion of the current state of knowledge regarding monkeypox virus with a special focus on innate immune response, immune evasion mechanisms and vaccination against the virus.

One of the main participants associated with the onset and maintenance of the porcine respiratory disease complex (PRDC) syndrome is porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus that has plagued the swine industry for 30 years. The development of effective PRRS vaccines, which deviate from live virus designs, would be an important step towards the control of PRRS. Potential vaccine antigens are found in the five surface proteins of the virus, which form covalent and multiple noncovalent interactions and possess hypervariable epitopes. Consequences of this complex surface structure include antigenic variability and escape from immunity, thus presenting challenges in the development of new vaccines capable of generating broadly sterilizing immunity. One potential vaccine target is the induction of antibody that disrupts the interaction between the macrophage CD163 receptor and the GP2, GP3, and GP4 heterotrimer that protrudes from the surface of the virion. Studies to understand this interaction by mapping mutations that appear following the escape of virus from neutralizing antibody identify the ectodomain regions of GP5 and M as important immune sites. As a target for antibody, GP5 possesses a conserved epitope flanked by N-glycosylation sites and hypervariable regions, a pattern of conserved epitopes shared by other viruses. Resolving this apparent conundrum is needed to advance PRRS vaccine development.

CD163, a macrophage-specific membrane scavenger receptor, serves as a cellular entry receptor for porcine reproductive and respiratory syndrome virus (PRRSV). The removal of scavenger receptor cysteine-rich (SRCR) domain 5 (SRCR5) of CD163 is sufficient to make transfected cells or genetically modified pigs resistant to PRRSV-1 and PRRSV-2 genotypes, and substitution of SRCR5 with SRCR8 from human CD163-like protein (hCD163L1) confers resistance to PRRSV-1 but not PRRSV-2 isolates. However, the specific regions within the SRCR5 polypeptide involved in PRRSV infection remain largely unknown. In this report, we performed mutational studies in order to identify which regions or amino acid sequences in the SRCR5 domain are critical for PRRSV infection. The approach used in this study was to make proline-arginine (PR) insertions along the SRCR5 polypeptide. Constructs were transfected into HEK293T cells, and then evaluated for infection with PRRSV-2 or PRRSV-1. For PRRSV-2, four PR insertions located after amino acids 8 (PR-9), 47 (PR-48), 54 (PR-55), and 99 (PR-100) had the greatest impact on infection. For PRRSV-1, insertions after amino acids 57 (PR-58) and 99 (PR-100) were critical. Computer simulations based on the crystal structure of SRCR5 showed that the mutations that affected infection localized to a similar region on the surface of the 3-D structure. Specifically, we found two surface patches that are essential for PRRSV infection. PR-58 and PR-55, which were separated by only three amino acids, had reciprocal effects on PRRSV-1 and PRRSV-2. Substitution of Glu-58 with Lys-58 reduced PRRSV-1 infection without affecting PRRSV-2, which partially explains the resistance to PRRSV-1 caused by the SRCR5 replacement with the homolog human SRCR8 previously observed. Finally, resistance to infection was observed following the disruption of any of the four conserved disulfide bonds within SRCR5. In summary, the results confirm that there are distinct differences between PRRSV-1 and PRRSV-2 on recognition of CD163; however, all mutations that affect infection locate on a similar region on the same face of SRCR5.

Significance: Myxoma virus (MYXV) is benign in the natural brush rabbit host but causes a fatal disease in European rabbits. Here, we demonstrate that MYXV M156 inhibited brush rabbit protein kinase R (bPKR) more efficiently than European rabbit PKR (ePKR). Because ePKR was not completely inhibited by M156, there was a depletion of short–half-life proteins like the nuclear factor kappa B (NF-κB) inhibitor IκBα, concomitant NF-κB activation and NF-κB target protein expression in ePKR-expressing cells. NF-κB pathway activation was blocked by either hypoactive or hyperactive M156 mutants. This demonstrates that maladaptation of viral immune antagonists can result in substantially different immune responses in aberrant hosts. These different host responses may contribute to altered viral dissemination and may influence viral pathogenesis.

Porcine reproductive and respiratory syndrome (PRRS) remains one of the most important infectious diseases affecting the global pig industry. The emergence of highly pathogenic PRRS virus 1 (PRRSV‐1) strains, first detected in northeastern Spain in 2020, poses new challenges for effective disease control. Despite their severe impact under field conditions, a comprehensive experimental characterization of these virulent strains has been lacking. In this study, we analyzed the genetic characteristics of the Lleida 029_22 strain, collected during a severe PRRSV‐1 outbreak, and evaluated its pathogenicity in pigs. Phylogenetic analysis revealed that the Lleida 029_22 strain belongs to a new clade describing multiple strains isolated during a PRRSV‐1 Rosalia‐related outbreak, with the highly pathogenic Italian strain PR40 identified as a common ancestor. In vitro , this strain replicated efficiently in porcine alveolar macrophages and PAM‐KNU cells, but not in MARC‐145 cells. To characterize the pathogenicity of this strain, 8‐week‐old piglets were inoculated with a 2 × 10 ⁵ TCID ₅₀ dose of the Lleida 029_22 strain via two inoculation routes—intramuscular (IM) and intranasal (IN). The IM‐infected pigs exhibited high levels of viremia and virus shedding, with 100% mortality recorded by 14 days post‐infection (dpi). These animals also showed significantly elevated levels of pro‐inflammatory cytokines, particularly IL‐6, and severe histopathologic lung lesions, correlating with the observed severe disease outcome. In contrast, IN‐infected pigs exhibited lower mortality (30%) and moderate clinical signs, with the surviving pigs fully recovering by the end of the 63‐day observation period. These pigs also exhibited prolonged viremia and viral shedding, with lower levels of pro‐inflammatory cytokines and neutralizing antibodies from 28 dpi. The IN infection closely mimicked the disease outcomes observed in Spanish farms experiencing outbreaks due to the high‐virulence Rosalia strain, while the IM infection highlighted the risks of iatrogenic transmission.