2021年 · 第03卷第02期

Influenza A (H3N2) virus has a faster evolution rate than other types of influenza viruses. In this study, whole genome sequencing was performed to better understand the molecular evolution of influenza H3N2 and the protective effect of influenza virus vaccine in Qinghai Province, China, in 2017. Complete sequences of eight gene segments of two seasonal influenza H3N2 isolates were sequenced and analyzed using DNASTAR and MEGA 6.06 software. Additionally, the three-dimensional structure of the HA protein was predicted using the SWISS-MODEL server. Phylogenetic and amino acid sequence analysis revealed that two Qinghai H3N2 isolates were typical low-pathogenic influenza viruses, and were relatively closely related to the 2016-2017 vaccine strain, 3C.2a-A/Hong Kong/4801/2014. The presence of several antigenic site substitutions (T131K, G/R142K, K160T and R261Q in the HA protein) were specific for the two Qinghai H3N2 virus strains. In addition, amino acid substitution of K160T at the glycosylation site of HA and H75P in PB1-F2 in Qinghai isolates might affect the antibody binding ability and virulence of the influenza virus. The presence of several antigenic site mutations in the Qinghai H3N2 isolates confirmed the evolution of circulating H3N2 strains.

Brucellosis is an important zoonotic infectious disease and is an important public health problem that causes serious economic consequences to the livestock industry. Brucella spp. comprise one of the most common pathogens causing laboratory-acquired infections (LAIs) and are becoming an increasingly important biosafety issue. To understand the significance of Brucella LAIs in China, related papers were search based on three Chinese databases (CNKI, Wanfang, and VIP), as well as PubMed. After assessment, 37 total cases were evaluated, including 27 students, seven laboratory technicians (one pregnant), two housekeeping staff, and one instructor. The age, sex, incubation period, pathogen detection results, and potential routes of infections were collected and analyzed. All LAIs occurred due to improper operations, inadequate biosafety training, and substandard laboratory safety conditions. Therefore, it is urgent to establish a comprehensive and systematic biosafety prevention/control system in laboratories to protect staff members from accidental exposures and LAIs; further, possible risks and control measures for the management of such infections were proposed.

With the number of Coronavirus Disease 2019 (COVID-19) cases soaring worldwide and limited vaccine availability for the general population in most countries, the monoclonal antibody (mAb) remains a viable therapeutic option to treat COVID-19 disease and its complications, especially in the elderly individuals. More than 50 monoclonal antibody-related clinical trials are being conducted in different countries around the world, with few of them nearing the completion of the third and fourth phase clinical trial. In view of recent emergency use authorization (EUA) from the FDA (Food and Drug Administration) of casirivimab and imdevimab, it is of importance that mAbs, already used to treat diseases such as Ebola and respiratory syncytial virus (RSV) infection, are discussed in scientific communities. This brief review discusses the mechanism of action and updates to clinical trials of different monoclonal antibodies used to treat COVID-19, with special attention paid to SARS-CoV-2 immune response in host cells, target viral structures, and justification of developing mAbs following the approval and administration of potential effective vaccine among vulnerable populations in different countries.

Prions are unconventional infectious agents that cause lethal transmissible neurodegenerative diseases in human and animals. Prions can be distinguished from other known pathogens by their lack of nucleic acids. The most essential process for prion propagation is conversion from normal cellular prion protein on the cell membrane to insoluble, limited protease digestion-resistant, pathogenic scrapie prion protein. For dozens of years, many pharmacological tools and interventions targeting different stages of disease progression have been developed and evaluated, and a few have been entered clinical trials. However, no approved prophylactic or therapeutic drugs for prion diseases are available. In this review, we summarize the current concepts in prion research and discuss advances in the research and development of drugs for the prevention and treatment of prion disease.

SFTS virus (SFTSV) is a novel bunyavirus, which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome (SFTS) in China in 2009, and was now prevalent in at least 25 provinces in China. SFTS was subsequently identified in South Korea and Japan in 2012. To explore the molecular evolution and genetic characteristics of this newly identified pathogen, we reported 72 whole genome sequences of SFTSV, and built a dataset of SFTSV genome sequences containing 292 L-segment, 302 M-segment and 502 S-segment. We clearly divided SFTSV into six genotypes, Genotype A-F. It was found that genotype F was the dominant epidemic genotype of Japan, South Korea, and Zhejiang province of China. The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province, and Genotype F was the most primitive one. Henan, Hubei, and Anhui provinces which are located in Dabie Mountain area were mainly epidemic of Genotype A, which emerged relatively late but distributed widely. A total of 37 recombination events were identified, making SFTSV with a high recombination frequency (L segment 5.1%, M segment 3.6%, S segment 0.8%) among negative-strand segmented RNA viruses. It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms. The reassortment virus and recombination in tick were both found for the first time. We also found many of genotype-specific mutation sites, 7 of which could be considered as potential molecular marker for genotype classification. This study promoted a more comprehensive understanding of the phylogeny and origin, and the genetic diversity of SFTSV, and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.

African swine fever virus (ASFV) is the causative agent of African swine fever, a highly fatal hemorrhagic disease of pigs, which has resulted in great economic losses to the global pork industry, especially in Asia. ASFV particles are comprised of multiple layers encompassing the genomic DNA. Though the capsid structure has been determined, very little is known about the structure of the core shell. The precursor polyprotein pp62 is the structural component of the core shell that gives rise to the p35 and p15 proteins. Herein, we describe the crystal structure of p15 at a resolution of 2.2 Å. The structure of p15 exhibits as a trimeric conformation that is mainly mediated by intermolecular disulfide bonds and supported by multiple hydrogen bond interactions. The button conformation on the surface of adjacent molecules may also play a role in trimeric formation of the ASFV p15. The center of the p15 trimer exhibits opposite electrostatic characteristics on each side. These findings benefit our understanding of ASFV core shell assembly and will aid in the design of antiviral drugs and vaccines.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid spread worldwide. In this study, we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2, using 22 virus genome sequences reported by three different laboratories in Morocco till June 7,2020, as well as 40,366 virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations, of which 30 were mis-sense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K, which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred once in Moroccan sequences, with no record in other sequences worldwide. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses belonging to Clade 20A, 9 to Clade 20B and 2 to Clade 20C, suggesting that the epidemic spread in Morocco did not display a predominant SARS-CoV-2 route. Therefore, multiple and unrelated introductions of SARS-CoV-2 into Morocco through different routes have occurred, giving rise to the diversity of virus genomes in the country. Further, in all probability, the SARS-CoV-2 circulated in a cryptic way in Morocco, starting from January 15, 2020 before the first case was officially discovered on March 2, 2020.