Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation.
甲型流感核蛋白 31 个和 450 个残基上的遗传变异影响病毒复制和翻译。
- 作者列表："Hung SJ","Hsu YM","Huang SW","Tsai HP","Lee LYY","Hurt AC","Barr IG","Shih SR","Wang JR
BACKGROUND:Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS:To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. RESULTS:The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. CONCLUSIONS:These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.
背景: 甲型流感病毒引起流行病/严重的大流行，构成巨大的全球健康威胁。在 8 个病毒RNA片段中，核蛋白 (NP) 的多种功能在病毒复制和转录中起重要作用。 方法: 为了了解NP如何促进病毒进化，我们分析了台湾H3N2 病毒es的NP基因和从流感研究数据库收集的 14,220 个NP序列。通过微基因组检测、病毒生长检测、病毒RNA和蛋白表达以及雪貂模型进一步分析鉴定的遗传变异，以分析其对病毒复制特性的影响。 结果: 台湾和全球序列的NP遗传分析显示了 1999-2018 年NP骨干随时间变化伴随特定残基置换的相似进化模式。除了con s erved重新s idue s，十五s poradic s ub s titution s被ob s erved的 31R、 377G和 450S s犬、更高的频率.我们发现 31R和 450S降低s ed polymera s e活性，而显性re s idue s (31 k和 450G) 具有较高的活性。31 k和 450G在体内外表现出较好的病毒翻译和复制。 结论: 这些发现表明进化中发现的变异在体外和体内调节病毒复制中具有作用。本研究表明，病毒进化过程中NP变异之间的相互作用值得未来关注。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.