One health advances最新文献

Continuously emergence of human infection with avian influenza A virus poses persistent threat to public health, as illustrated in zoonotic H5N1/6 and H7N9 infections. The recent surge of infection to farmed mink by multiple subtypes of avian influenza A viruses in China highlights the role of mink in the ecology of influenza in this region. Serologic studies suggested that farmed mink in China are frequently infected with prevailing human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Moreover, genetic analysis from the sequences of influenza viruses from mink showed that several strains acquired mammalian adaptive mutations compared to their avian counterparts. The transmission of SARS-CoV-2 from mink to human alerts us that mink may serve as an intermediate host or reservoir of some emerging pathogens. Considering the high susceptibility to different influenza A viruses, it is possible that mink in endemic regions may play a role as an "mixing vessel" for generating novel pandemic strain. Thus, enhanced surveillance of influenza viruses in mink should be urgently implemented for early warning of potential pandemic.

The human intestinal tract is considered the most important reservoir of the opportunistic pathogens, including Pseudomonas aeruginosa, which is often overlooked but critical due to its antimicrobial resistance and virulence. Public health interventions to control this pathogen require a comprehensive understanding of its epidemiology and genomics.  In the current study, we identified P. aeruginosa strains from 2,605 fecal samples collected between 2021 to 2022. Among these samples, 574 were from ICU inpatients in Zhejiang province, while 2,031 were obtained from healthy individuals residing in ten different provinces in China. The prevalence of P. aeruginosa intestinal carriage was found to be higher in ICU inpatients (10.28%, 95% CI: 7.79%-12.76%) than that in healthy individuals (3.99%, 81/2,031, 95% CI: 3.14%-4.84%). Similarly, the prevalence of carbapenem-resistant P. aeruginosa (CRPA) was higher in ICU inpatients (32.2%) compared to healthy individuals (7.41%). The population structure analysis of our isolates revealed a predominantly non-clonal distribution, with 41 distinct sequence types identified among 59 P. aeruginosa isolates from ICU inpatients and 38 different STs among 81 P. aeruginosa isolates from healthy individuals. These findings suggest that the individual acquisition of P. aeruginosa is more frequent than patient-to-patient transmission, as evidenced by the polyclonal population structure. Antimicrobial susceptibility testing and genome analysis indicated that P. aeruginosa strains from ICU inpatients exhibited significantly higher resistance rates to most antimicrobials and harbored a greater number of acquired resistance genes compared to strains from healthy individuals. Notably, in ICU inpatients, we identified three isolates of ST463, all of which shared the conserved Tn3-TnpR-ISKpn8-bla_KPC-ISKpn6 genetic context. Additionally, five isolates carrying the qacE gene were also identified, these findings suggest that small-scale transmission events may still occur within the ICU setting, posing significant challenges for clinical management. With regard to virulence factors, we observed similar profiles between the two groups, except for phzA2, phzB2, and pilA, which were statistically higher in isolates from healthy individuals. This may be because the accumulating resistance mutations in ICU-derived P. aeruginosa are linked to a decrease in virulence.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen for the global pork industry. Although modified live virus (MLV) vaccines are commonly used for PRRSV prevention and control,  they still carry a risk of infecting the host and replicating in target cells, thereby increasing the likehood of virus recombination and reversion to virulence. In this study, we inserted the target sequence of miR-142 into the nsp2 hypervariable region of PRRSV to inhibit viral replication in its host cells of pigs, with the aim of achieving virus attenuation. The chimeric virus RvJX-miR-142t was successfully rescued and retained its growth characteristics in MARC-145 cells. Furthermore, it did not replicate in MARC-145 cells transfected with miRNA-142 mimic. We also observed limited replication ability of RvJX-miR-142t in pulmonary alveolar macrophages, which are the main cell types that PRRSV infects. Our animal inoculation study showed that pigs infected with RvJX-miR-142t displayed less severe clinical symptoms, lower viremia titers, lighter lung lesions, and significantly lower mortality rates during the first 7 days post-inoculation, in comparison to pigs infected with the backbone virus RvJXwn. We detected a partially deletion of the miR-142 target sequence in the RvJX-miR-142t genome at 14 dpi. It is highly possible that the reversion of viral virulence observed in the later timepoints of our animal experiment was caused by that. Our study provided a new strategy for attenuating PRRSV and confirmed its effectiveness. However, further studies are necessary to increase the stability of this virus under host selection pressure.

Potent neutralizing antibodies (nAbs) against SARS-CoV-2 are a promising therapeutic against the ongoing COVID-19 pandemic. However, the continuous emergence of neutralizing antibody escape variants makes it challenging for antibody therapeutics based on monospecific nAbs. Here, we generated an IgG-like bispecific antibody (bsAb), Bi-Nab, based on a pair of human neutralizing antibodies targeting multiple and invariant sites of the spike receptor binding domain (RBD): 35B5 and 32C7. We demonstrated that Bi-Nab exhibited higher binding affinity to the Delta spike protein than its parental antibodies and presented an extended inhibition breadth of preventing RBD binding to angiotensin-converting enzyme 2 (ACE2), the cellular receptor of SARS-CoV-2. In addition, pseudovirus neutralization results showed that Bi-Nab improved the neutralization potency and breadth with a lower half maximum inhibitory concentration (IC₅₀) against wild-type SARS-CoV-2, variants being monitored (VBMs) and variants of concern (VOCs). Notably, the IgG-like Bi-Nab enhanced the neutralizing activity against Omicron variants with potent capabilities for transmission and immune evasion in comparison with its parental monoclonal antibody (mAb) 32C7 and a cocktail (with the lowest IC₅₀ values of 31.6 ng/mL against the Omicron BA.1 and 399.2 ng/mL against the Omicron BA.2), showing evidence of synergistic neutralization potency of Bi-Nab against the Omicron variants. Thus, Bi-Nab represents a feasible and effective strategy against SARS-CoV-2 variants of concern.