Human ACE2 protein is a molecular switch controlling the mode of SARS-CoV-2 transmission.

BACKGROUND: Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the lungs and is upregulated after SARS-CoV-2 infection. How such a hACE2-limited pulmonary environment supports efficient virus transmission and how dynamic hACE2 expression affects SARS-CoV-2 infection are unclear. METHODS: We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission. RESULTS: We demonstrated that the hACE2 expression level controls the mode of SARS-CoV-2 transmission. The hACE2-limited cells have an advantage for SARS-CoV-2 shedding, which leads to cell-free transmission. By contrast, enhanced hACE2 expression facilitates the SARS-CoV-2 cell-to-cell transmission. Furthermore, this cell-to-cell transmission is likely facilitated by hACE2-containing vesicles, which accommodate numerous SARS-CoV-2 virions and transport them to neighboring cells through intercellular extensions. CONCLUSIONS: This hACE2-mediated switch between cell-free and cell-to-cell transmission routes provides SARS-CoV-2 with advantages for either viral spread or evasion of humoral immunity, thereby contributing to the COVID-19 pandemic and pathogenesis.

Association between Glyphosate Exposure and Erythrograms in a Representative Sample of US Adults: NHANES 2013-2014.

Glyphosate is the most commonly utilized herbicide globally, and a growing body of experimental research has linked its exposure to red blood cell damage. However, the potential toxicity of glyphosate exposure on erythrocytes in the general population remains poorly understood. Therefore, we analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) of 1466 adults (≥ 18 years) to explore the potential relationship between glyphosate exposure and erythrocyte profiles. Our results indicated a significant negative association between urinary glyphosate levels and hemoglobin (Hb) and hematocrit (Hct) in multiple regression analysis, with ß coefficients of -0.157 (S.E. = 0.055, P = 0.012) and -0.431 (S.E. = 0.195, P = 0.043), respectively. Additionally, the odds ratio showed a significant increase in individuals with anemia with a one-unit increase in ln-glyphosate levels (odds ratio = 1.523 (95% CI = 1.301 - 1.783), P < 0.001 in the final model). The negative correlation between glyphosate and Hb was more pronounced in subjects older than 60 years, non-Hispanic white ethnicity, lower income, and those with a body mass index (BMI) < 25 and ≥ 30. In conclusion, our results provide preliminary evidence of a plausible association between glyphosate exposure and anemia in a subset of the adult population in the United States. However, further research is necessary to understand the underlying mechanisms and clinical implications of this association.

Parenterally Administered Porcine Epidemic Diarrhea Virus-Like Particle-Based Vaccine Formulated with CCL25/28 Chemokines Induces Systemic and Mucosal Immune Protectivity in Pigs.

Generation of a safe, economical, and effective vaccine capable of inducing mucosal immunity is critical for the development of vaccines against enteric viral diseases. In the current study, virus-like particles (VLPs) containing the spike (S), membrane (M), and envelope (E) structural proteins of porcine epidemic diarrhea virus (PEDV) expressed by the novel polycistronic baculovirus expression vector were generated. The immunogenicity and protective efficacy of the PEDV VLPs formulated with or without mucosal adjuvants of CCL25 and CCL28 (CCL25/28) were evaluated in post-weaning pigs. While pigs intramuscularly immunized with VLPs alone were capable of eliciting systemic anti-PEDV S-specific IgG and cellular immunity, co-administration of PEDV VLPs with CCL25/28 could further modulate the immune responses by enhancing systemic anti-PEDV S-specific IgG, mucosal IgA, and cellular immunity. Upon challenge with PEDV, both VLP-immunized groups showed milder clinical signs with reduced fecal viral shedding as compared to the control group. Furthermore, pigs immunized with VLPs adjuvanted with CCL25/28 showed superior immune protection against PEDV. Our results suggest that VLPs formulated with CCL25/28 may serve as a potential PEDV vaccine candidate and the same strategy may serve as a platform for the development of other enteric viral vaccines.