Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.

Introduction: Sepsis represents a critical medical condition that arises due to an imbalanced host reaction to infection. Central to its pathophysiology are cytokines. However, observational investigations that explore the interrelationships between circulating cytokines and susceptibility to sepsis frequently encounter challenges pertaining to confounding variables and reverse causality.Methods: To elucidate the potential causal impact of cytokines on the risk of sepsis, we conducted two-sample Mendelian randomization (MR) analyses. Genetic instruments tied to circulating cytokine concentrations were sourced from genome-wide association studies encompassing 8,293 Finnish participants. We then evaluated their links with sepsis and related outcomes using summary-level data acquired from the UK Biobank, a vast multicenter cohort study involving over 500,000 European participants. Specifically, our data spanned 11,643 sepsis cases and 474,841 controls, with subsets including specific age groups, 28-day mortality, and ICU-related outcomes.Results and Discussion: MR insights intimated that reduced genetically-predicted interleukin-10 (IL-10) levels causally correlated with a heightened sepsis risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.52-0.90, P=0.006). An inverse relationship emerged between monocyte chemoattractant protein-1 (MCP-1) and sepsis-induced mortality. Conversely, elevated macrophage inflammatory protein 1 beta (MIP1B) concentrations were positively linked with both sepsis incidence and associated mortality. These revelations underscore the causal impact of certain circulating cytokines on sepsis susceptibility and its prognosis, hinting at the therapeutic potential of modulating these cytokine levels. Additional research is essential to corroborate these connections.

Crab lice (Phthirus pubis) infestation can occur at any age, to either males or females, and across all regions of the world. However, cases involving the eyelashes and adjacent eyelids (phthiriasis palpebrarum) are rare. Usually occurring as a sexually transmitted disease, crab lice can be spread by poor hygiene or in a dirty environment through direct contact with contaminated skin (hands) or textiles (towels and clothing). A 50-year-old woman presented to our hospital with a 2-wk history of chronic eyelid pain and itching in the right eye, which exacerbated in the evening hours and which had not resolved following a 1-wk course of antibiotics and corticosteroid ointments (for blepharitis diagnosis from another hospital). A careful ophthalmic slit-lamp and light microscope examination revealed multiple crab lice and nits on the right upper eyelashes; the right and left lower eyelashes were normal. Following the new diagnosis of phthiriasis palpebrarum, the patient was treated by removing the affected eyelashes, the crab lice, and their nits completely. Additionally, the eyelids were washed once with povidone-iodine. A follow-up examination at 2 wk later showed complete resolution of symptoms and no evidence of re-infection. This case emphasizes the importance of correct diagnosis and complete removal of eyelashes, crab lice and nits to cure phthiriasis palpebrarum.

Highly pathogenic avian influenza (HPAI) H5 viruses have recently been documented in mammals including humans, posing a major threat to global public health. To prevent a potential H5 pandemic, it is critical to elucidate the antigenic evolutionary pattern and identify key drivers underlying its evolution. In this work, we construct a comprehensive antigenic map of H5 influenza viruses spanning their evolutionary history and classified three antigenic clusters with no cross-neutralization. The first corresponds to ancestral clades, the second to 2.3.4.4* clades being predominant since 2010, and the third to 2.3.4.4 h clade. Despite the gradually increasing genetic distances from ancestral to 2.3.4.4* to 2.3.4.4 h, their antigenic evolution does not follow the same progressive pattern: the antigenic distance between 2.3.4.4 h and ancestral is smaller than that between 2.3.4.4* and ancestral. This divergence is associated with two distinct mutation patterns at six key amino acid positions: (1) persistent mutations at positions 88 (N > R > S), 199 (D > N > S), and 205 (K > N > D), and (2) reversible mutations at positions 131 (Q > L > Q), 139 (S > P > S), and 289 (N > H > N). These findings not only reveal the antigenic evolution mechanism of H5 influenza, but also provide important guidance for vaccine strain selection and broad-spectrum vaccine development.

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections in infants and the elderly. Previously, most RSV vaccine antigen design strategies have focused on the stability of the prefusion (PreF) protein trimer conformation. We hypothesized that the RSV monomer might serve as a vaccine candidate immunogen. Here, we constructed an immunofocusing-based RSV F protein Q74 truncated monomer by truncating the RSV F protein and retaining only the head and neck regions. The structural prediction and protein antigenicity characterization of Q74 truncated monomer both indicated that it could bind to the antigenic site Ø-specific antibody D25, suggesting that this immunogen retained the structural features of PreF. In addition, the Q74 truncated monomer not only induced neutralizing and binding antibodies with a strength comparable to that of DS-Cav1, but also focused the immune response on antigenic site Ø and site II. In summary, we found that the RSV F protein monomer designed based on immunofocusing could induce relatively immunogenicity and immune protection, providing a design strategy for RSV vaccines.