Linlin Zhou

Bio: Linlin Zhou is an academic researcher from University of Hong Kong. The author has contributed to research in topics: Medicine & Structural basin. The author has an hindex of 1, co-authored 1 publications receiving 381 citations.

The genesis and source of the H7N9 influenza viruses causing human infections in China

Abstract: A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

Emergence of a SARS-CoV-2 Omicron Subvariant BA.2.2 with a 454-Nucleotide Genomic Deletion — Sichuan Province, China, May 10, 2022

Abstract: On May 9, 2022, 3 local residents in Guang’an City, Sichuan Province, tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and were diagnosed as asymptomatic infections with coronavirus disease 2019 (COVID-19) in a local outbreak, and as of May 14, a total of 20 confirmed cases and 398 asymptomatic infections were reported. Whole genome sequencing was performed directly on the nasal and throat swab specimens from the initial three asymptomatic infected individuals using the Illumina MiSeq platform (Illumina, San Diego, CA, USA). The complete genome sequences of 3 SARS-CoV-2 strains, named SC1215, SC1216, and SC1217, were obtained. The sequence of SC1217 has been deposited in the GISAID database (under the accession number EPI_ISL_12725020). Phylogenetic analysis (maximum likelihood method) revealed that the 3 local strains clustered together to form a monophyletic clade belonging to the Omicron BA.2.2 sublineage (Figure 1) (1–2). The BA.2.2 sublineage was derived from the Omicron BA.2 lineage (3) and may have originated in Hong Kong Special Administrative Region (SAR) with predominant transmission to the mainland of China, Japan, Australia, and the United Kingdom (2). Genomic analysis revealed a 454 nucleotide (nt) deletion in the SARS-COV-2 genome at nucleotide positions 27,689–28,142, and this result was further validated by Sanger sequencing (Figure 2). Sequencing of 41 clinical specimens from the local outbreak in Guang’an by May 14 had also detected the 454-nt deletion. Further analysis revealed that the 454-nt deletion resulted in a 71-nt deletion at the 3’ end of ORF7a gene, a complete deletion of ORF7b gene (132-nt) and the intergenic region of ORF7b/8 (6-nt) gene, and a 249-nt deletion at the 5’ end of ORF8 gene. As of May 12, 2022, 2,787 sequences in the GISAID database were Omicron BA.2.2 sublineage, but no such long 454-nt deletion were found. ORF7a, ORF7b, and ORF8, which encode accessory proteins of SARS-CoV-2, are important for the interaction of SARS-CoV-2 with the host. Previous studies have shown that ORF7a protein binds to human monocytes, decrease antigen presentation ability, and induces dramatic expression of pro-inflammatory cytokines (4–5). Deletion of ORF8 may lead to a milder infection and a more efficient immune response to SARS-CoV-2 (6). Further experiments are needed on whether and how this 454-nt deletion affects the infectivity and pathogenicity of the virus, and epidemiological and genomic surveillance are needed to monitor its potential further transmission.

Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia

Abstract: Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS-CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus.

Role of receptor binding specificity in influenza A virus transmission and pathogenesis

Abstract: The recent emergence of a novel avian A/H7N9 influenza virus in poultry and humans in China, as well as laboratory studies on adaptation and transmission of avian A/H5N1 influenza viruses, has shed new light on influenza virus adaptation to mammals. One of the biological traits required for animal influenza viruses to cross the species barrier that received considerable attention in animal model studies, in vitro assays, and structural analyses is receptor binding specificity. Sialylated glycans present on the apical surface of host cells can function as receptors for the influenza virus hemagglutinin (HA) protein. Avian and human influenza viruses typically have a different sialic acid (SA)-binding preference and only few amino acid changes in the HA protein can cause a switch from avian to human receptor specificity. Recent experiments using glycan arrays, virus histochemistry, animal models, and structural analyses of HA have added a wealth of knowledge on receptor binding specificity. Here, we review recent data on the interaction between influenza virus HA and SA receptors of the host, and the impact on virus host range, pathogenesis, and transmission. Remaining challenges and future research priorities are also discussed.

Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus

Abstract: The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant’s internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010–2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.