Zi Li

Bio: Zi Li is an academic researcher from Chinese Center for Disease Control and Prevention. The author has contributed to research in topics: Virus & Influenza A virus subtype H5N1. The author has an hindex of 14, co-authored 50 publications receiving 899 citations. Previous affiliations of Zi Li include National Health and Family Planning Commission.

Indications that Live Poultry Markets Are a Major Source of Human H5N1 Influenza Virus Infection in China

Abstract: Human infections of H5N1 highly pathogenic avian influenza virus have continued to occur in China without corresponding outbreaks in poultry, and there is little conclusive evidence of the source of these infections Seeking to identify the source of the human infections, we sequenced 31 H5N1 viruses isolated from humans in China (2005 to 2010) We found a number of viral genotypes, not all of which have similar known avian virus counterparts Guided by patient questionnaire data, we also obtained environmental samples from live poultry markets and dwellings frequented by six individuals prior to disease onset (2008 and 2009) H5N1 viruses were isolated from 4 of the 6 live poultry markets sampled In each case, the genetic sequences of the environmental and corresponding human isolates were highly similar, demonstrating a link between human infection and live poultry markets Therefore, infection control measures in live poultry markets are likely to reduce human H5N1 infection in China

Genesis and Spread of Newly Emerged Highly Pathogenic H7N9 Avian Viruses in Mainland China.

Abstract: The novel low-pathogenic avian influenza A H7N9 viruses (LPAI H7N9 viruses) have been a threat to public health since their emergence in 2013 because of the high rates of mortality and morbidity that they cause. Recently, highly pathogenic variants of these avian influenza A H7N9 viruses (HPAI H7N9 viruses) have emerged and caused human infections and outbreaks among poultry in mainland China. However, it is still unclear how the HPAI H7N9 virus was generated and how it evolved and spread in China. Here, we show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze River Delta region and spread southward to the Pearl River Delta region, possibly through live poultry trade. After introduction into the Pearl River Delta region, the origin LPAI H7N9 virus acquired four amino acid insertions in the hemagglutinin (HA) protein cleavage site and mutated into the HPAI H7N9 virus in late May 2016. Afterward, the HPAI H7N9 viruses further reassorted with LPAI H7N9 or H9N2 viruses locally and generated multiple different genotypes. As of 14 July 2017, the HPAI H7N9 viruses had spread from Guangdong Province to at least 12 other provinces. The rapid geographical expansion and genetic evolution of the HPAI H7N9 viruses pose a great challenge not only to public health but also to poultry production. Effective control measures, including enhanced surveillance, are therefore urgently needed.IMPORTANCE The LPAI H7N9 virus has caused five outbreak waves in humans and was recently reported to have mutated into highly pathogenic variants. It is unknown how the HPAI H7N9 virus originated, evolved, and disseminated in China. In this study, we comprehensively analyzed the sequences of HPAI H7N9 viruses from 28 human and 21 environmental samples covering eight provinces in China that were taken from November 2016 to June 2017. The results show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze River Delta region. However, the insertion of four amino acids into the HA protein cleavage site of an LPAI H7N9 virus occurred in late May 2016 in the Pearl River Delta region. The mutated HPAI H7N9 virus further reassorted with LPAI H7N9 or H9N2 viruses that were cocirculating in poultry. Considering the rapid geographical expansion of the HPAI H7N9 viruses, effective control measures are urgently needed.

Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017

Abstract: With no or low virulence in poultry, avian influenza A(H7N9) virus has caused severe infections in humans. In the current fifth epidemic wave, a highly pathogenic avian influenza (HPAI) H7N9 virus emerged. The insertion of four amino acids (KRTA) at the haemagglutinin (HA) cleavage site enabled trypsin-independent infectivity of this virus. Although maintaining dual receptor-binding preference, its HA antigenicity was distinct from low-pathogenic avian influenza A(H7N9). The neuraminidase substitution R292K conferred a multidrug resistance phenotype.

Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in China

Abstract: Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas, and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and the continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry and supervision of poultry movements should be strengthened. IMPORTANCE Since its occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have been demonstrating the continuing pandemic threat posed by the current influenza ecosystem in China. As the viruses are silently circulated in poultry, with potentially severe outcomes in humans, H7N9 virus activity in humans in China is very important to understand. In this study, we identified a newly emerged H7N9 outbreak source in the Pearl River Delta region. Both sources in the Yangtze River Delta region and the Pearl River Delta region have been established and found to be responsible for the H7N9 outbreaks in mainland China.

Generation, Characterization and Epitope Mapping of Two Neutralizing and Protective Human Recombinant Antibodies against Influenza A H5N1 Viruses

Abstract: Background: The development of new therapeutic targets and strategies to control highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is urgently needed. Broadly cross-neutralizing recombinant human antibodies obtained from the survivors of H5N1 avian influenza provide an important role in immunotherapy for human H5N1 virus infection and definition of the critical epitopes for vaccine development. Methodology/Principal Findings: We have characterized two recombinant baculovirus-expressed human antibodies (rhAbs), AVFluIgG01 and AVFluIgG03, generated by screening a Fab antibody phage library derived from a patient recovered from infection with a highly pathogenic avian influenza A H5N1 clade 2.3 virus. AVFluIgG01 cross-neutralized the most of clade 0, clade 1, and clade 2 viruses tested, in contrast, AVFluIgG03 only neutralized clade 2 viruses. Passive immunization of mice with either AVFluIgG01 or AVFluIgG03 antibody resulted in protection from a lethal H5N1 clade 2.3 virus infection. Furthermore, through epitope mapping, we identify two distinct epitopes on H5 HA molecule recognized by these rhAbs and demonstrate their potential to protect against a lethal H5N1 virus infection in a mouse model. Conclusions/Significance: Importantly, localization of the epitopes recognized by these two neutralizing and protective antibodies has provided, for the first time, insight into the human antibody responses to H5N1 viruses which contribute to the H5 immunity in the recovered patient. These results highlight the potential of a rhAbs treatment strategy for human H5N1 virus infection and provide new insight for the development of effective H5N1 pandemic vaccines.

Sampling: Design and Analysis

Abstract: In his seminal book, Shewhart (1931) makes no demand on the distribution of the characteristic to be plotted on a control chart. How then can we explain the idea that normality is, if not required, at least highly desirable? I believe that it has come about through the many statistical studies of control-chart behavior. If one is to study how a control chart behaves, it is necessary to relate it to some distribution. The obvious choice is the normal distribution because of its ubiquity as a satisfactory model. This is bolstered by the existence of the Central Limit Theorem.

Human Infection with an Avian H9N2 Influenza A Virus in Hong Kong in 2003

Abstract: Avian H9N2 influenza A virus has caused repeated human infections in Asia since 1998. Here we report that an H9N2 influenza virus infected a 5-year-old child in Hong Kong in 2003. To identify the possible source of the infection, the human isolate and other H9N2 influenza viruses isolated from Hong Kong poultry markets from January to October 2003 were genetically and antigenically characterized. The findings of this study show that the human H9N2 influenza virus, A/Hong Kong/2108/03, is of purely avian origin and is closely related to some viruses circulating in poultry in the markets of Hong Kong. The continued presence of H9N2 influenza viruses in poultry markets in southern China increases the likelihood of avian-to-human interspecies transmission.

Beyond natural antibodies: the power of in vitro display technologies

Abstract: In vitro display technologies, best exemplified by phage and yeast display, were first described for the selection of antibodies some 20 years ago. Since then, many antibodies have been selected and improved upon using these methods. Although it is not widely recognized, many of the antibodies derived using in vitro display methods have properties that would be extremely difficult, if not impossible, to obtain by immunizing animals. The first antibodies derived using in vitro display methods are now in the clinic, with many more waiting in the wings. Unlike immunization, in vitro display permits the use of defined selection conditions and provides immediate availability of the sequence encoding the antibody. The amenability of in vitro display to high-throughput applications broadens the prospects for their wider use in basic and applied research.

Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China.

Abstract: Objective: Narcolepsy is caused by the loss of hypocretin/orexin neurons in the hypothalamus, which is likely the result of an autoimmune process. Recently, concern has been raised over reports of narcolepsy in northern Europe following H1N1 vaccination. Methods: The study is a retrospective analysis of narcolepsy onset in subjects diagnosed in Beijing, China (1998– 2010). Self-reported month and year of onset were collected from 629 patients (86% children). Graphical presentation, autocorrelations, chi-square, and Fourier analysis were used to assess monthly variation in onset. Finally, 182 patients having developed narcolepsy after October 2009 were asked for vaccination history. Results: The occurrence of narcolepsy onset was seasonal, significantly influenced by month and calendar year. Onset was least frequent in November and most frequent in April, with a 6.7-fold increase from trough to peak. Studying year-to-year variation, we found a 3-fold increase in narcolepsy onset following the 2009 H1N1 winter influenza pandemic. The increase is unlikely to be explained by increased vaccination, as only 8 of 142 (5.6%) patients recalled receiving an H1N1 vaccination. Cross-correlation indicated a significant 5- to 7-month delay between the seasonal peak in influenza/cold or H1N1 infections and peak in narcolepsy onset occurrences. Interpretation: In China, narcolepsy onset is highly correlated with seasonal and annual patterns of upper airway infections, including H1N1 influenza. In 2010, the peak seasonal onset of narcolepsy was phase delayed by 6 months relative to winter H1N1 infections, and the correlation was independent of H1N1 vaccination in the majority of the sample. ANN NEUROL 2011;70:410–417