Brief Introduction

There are five major research fields in Wuhan Institute of Virology, Chinese Academy of Sciences: 1.etiology and epidemiology of emerging infectious diseases; 2.molecular virology; 3. immunovirology; 4.analytical pathogen microbiology; and 5.agricultural and environmental microbiology.

1.Etiology and Epidemiology of Emerging Infectious Diseases
(1) Background
Emerging Infectious Diseases (EID) are among the major threats to public health around the world. One of the major challenges for prevention and control of EIDs is the unpredictable of EID outbreak. We are always not ready for EID outbreak, especially lack of the essential diagnostic techniques and methods, and even the basic knowledge of the pathogens. Among the EID pathogens, more than 70% origin from or transmit by wildlife (e.g. bat and bird)or insect vectors (e.g. tick and mosquito) and cause high mortality. Through systemic study of wildlife viruses we could not only uncover the animal origin and transmission of the known human viruses, but also build-up knowledge on animal viruses, especially uncharacterized viruses and be prepared in advance for outbreak of new EID. This field is under fast development, which has been further enhanced with the usage of advanced technology such as high-throughput sequencing in recent years, but still far more behind for EID control requirements.
This research area was built up during the outbreak of the SARS in 2002-2003 in China. Since then, a number of research groups were recruited or updated their interests to study on diverse pathogens of infectious diseases including SARS-CoV, influenza viruses, hemorrhagic fever viruses and antibiotic resistant-tuberculosis. With the construction of the national high level biosafety laboratory platforms it is also the bounden duty for the institute to study highly pathogenic agents, which currently occur in China and potentially imported aboard. This team now has full capability for the quickly response to EID outbreak regarding the pathogen detection, identification and pathogenesis studies.

(2) Objectives and scientific significance
This area focuses on pathogens causing EID, including: 1) Origin and genetic evolution of EID pathogens; 2) Identification of novel or unknown pathogens; 3) Risk assessment of novel pathogens in wildlife to human and domestic animals; 4) Molecular mechanism of interspecies transmission of zoonotic pathogens. The research on etiology and epidemiology of emerging infectious diseases will provide extensive knowledge of diverse pathogens carried by wildlife in China and useful technical support for the prevention and control of emerging infectious disease transmitted by wildlife.

2.Molecular Virology

(1) Background
WIV, whose research spans from agriculture viruses to human viruses, is the only institute in China focusing on comprehensive research on virology. WIV traditionally focused on agricultural virology and keeps on making important advances in the field of baculovirus. To meet the country’s increasing demanding for better healthcare, we began to recruit faculties with expertise on clinically important viruses including HBV, HCV, HIV, Influenza virus, EV71, and herpesviruses since 2004. Accordingly, the emphasis of the area transits to study different aspects of viral pathogenesis. So far, members in this area have made significant contributions to understand the mechanisms of viral pathogenesis, For example, an immune competent mouse model for HCV natural infection has been established, high resolution structure of the full-length flavivirus non-structural protein NS5 has been solved, new platforms to study pathogenesis of viral diseases were established including stem cell model for herpesvirus infection and 3-D culture cell model for HBV. Overall, this research area is in a better shape to uncover pathogenesis of viral diseases, so as to improve diagnostics and therapeutics. 
(2) Objectives and scientific significance
The ultimate objective in this area is to reveal the mechanism(s) for virus replication (including virus entry, viral genome replication, virion assembly and release) and to elucidate the pathogenesis of major viral diseases. The specific goals include but do not limit to the following areas:
1) To investigate the structure and function of viral protein in the context of viral
1) To study the biology/ genetics of viruses and their interaction with hosts.
3) To understand the molecular mechanism of viral evolution and transmission.
4) To study the pathogenic mechanism of acute and persistent viral infection.

(1) Background
Virus-host interaction plays a critical role in the pathogenesis and outcome of infectious diseases. Understanding of the underlying mechanisms has not only advanced the biology significantly, but also benefited greatly the development of biotechnology and related diagnosis and treatment of viral diseases. IN principle, how immune cells sense and initiate the innate signaling in response to viruses, and how the immune system responds during acute, latent and persistent viral infection, remain the core of immunovirological studies. In particular, several frontiers yet tough questions remain for this area. 1) The early events of HIV-1 infection at mucosae remain elusive. Identification of viral and cellular factors involved in HIV-1 entry and transmission at mucosal surfaces is critical for understanding viral pathogenesis and for the development of effective prevention strategies. Moreover, how IgA, the predominant mucosal antibody, mediates defence functions at different anatomic levels in relation to mucosal epithelium, particularly for IgA intracellular neutralization of viruses, is not fully understood. 2) Upon breaking through the mucosal barrier, the interplay between viral and host gene programs determine the homeostasis thus outcome of the infection. Viral genomes are recognized by membranous TLRs and/or cytosolic RLRs, which trigger a spectrum of interferons (IFNs) and pro-inflammatory cytokines responses. However, the inter-regulatory circuit of antiviral IFN and TNF/IL-1 signalling has far from been elucidated. 3) Immunopathology lies in the area of pathogenesis of virus infectious diseases. However, the molecular and cellular bases for the onset and progression of chronic Hepatitis C, for example, is still murky due to the asymptomatic nature of infection, and the lack of appropriate small animal model that can recapitulate temporally the immune response in the lesion. Thus, understanding of the mechanisms of self-limiting and persistent HCV infection would help delineating the underlying immunopathological events. 4) Antibody-based therapeutics works effectively against certain viral infections. It has become delicate and challenge enough to develop both full-size antibodies and their functional fragments, to understand functionality of antibodies in general and to apply to prevention and treatment of viral infections.
(2) Objectives and scientific significance
The objectives for research in this area include mainly: 1) to study mucosal immune response to viral infection of reproductive tract and airways, aiming to develop novel mucosal vaccines targeting viral entry and transmission; 2) to pinpoint the interactions of viral and host gene programs in order to depict the network of innate immune recognition and response; 3) to understand the immune tolerance and immunopathology of chronic viral infection, aiming to develop tools to intervene the inflammatory malignancy and to eradicate viruses; and (4) to understand the structure-function of antibodies, aiming to design more potent and effective antibody-based therapeutics. The outcome will be instrumental in understanding the mechanisms of HIV-1 and Measles mucosal infection, which can be translated to development of topical microbicides and mucosal vaccines. The gained fundamentals of innate signalling and regulatory network will add up to the understanding of both basics of antiviral innate immunity and mechanisms of viral evasion. The determination of inflammatory response and immune tolerance to HCV will provide generalizable insight of immunopathology of chronic RNA viruses infection.

4.Analytical Pathogen Microbiology

(1) Background

Analytical science with capabilities of ultra sensitivity, high throughput, real-time and in vivo (live cells and animals) provides new methods and insights into pathogen research and diagnosis, and drives the biological sciences. Analytical biotechnology research was initiated in WIV in 1982. We have developed a series of biosensors by exploiting various microbial components as sensing elements, e.g. whole cell microbial sensors for BOD, enzyme electrodes for fermentation control and blood glucose, antibody peizoelecronic sensors for Bacillus anthrax, gene optical sensors for HBV and multi pathogens, etc. The systematic innovative studies of biosensors in WIV win the international reputation and the team has become the major or sole Chinese member of the international organizing committee of the World Congress on Biosensors’ 2008, 2010, 2012 and 2014. Dr. Zhang Xian-En, the founder of biosensor research in the institute, was assigned as director general for basic research in the China Ministry of S&T. Under his guidance, the young scientists teamed up and continued the career. In recent years, the institute has increasingly emphasized human pathogen research, which oriented our research more focusing on pathogens. Therefore, we began studies in analytical pathogen microbiology. Persistent interdisciplinary studies (integration of microbiology and virology, chemistry, nanotechnology and synthetic biology) had made our research unique characteristics. Especially, we are the pioneer in China who integrates nanotechnology with virology in development of nano-biosensors. At present, our research consists of four aspects: viral-nanostructure-enabled techniques, virology and intracellular molecular imaging, M. tuberculosis whole proteome microarray and antibody chip, and sensitive and rapid detection of pathogenic microbes. During the past five years, we have made significant progresses in these directions.

(2) Objectives and scientific significance
Our objective is to develop ultra sensitive, high-throughput, rapid, real-time and in vivo analytical technologies for solving fundamental scientific problems of pathogen microbiology/virology and meeting the needs of clinical diagnosis. Advanced analytical technologies will drive the breakthrough in fundamental scientific research and provide better clinical diagnostics. Real-time and in vivo imaging technologies will offer in situ visualization of pathogen–host interactions to reveal mechanisms of pathogenesis. High throughput will enable systematic finding of the potential biomarkers, antigens and drug targets. Highly sensitive and rapid analytical technologies will provide early diagnosis of infectious diseases and timely information for proper treatment of infections, reducing the cost and saving more lives.

5.Agricultural and Environmental Microbiology

(1) Background
The intensive application of chemical pesticides is a major reason for environmental pollutions. Meeting the demands of the sustainable development of Chinese national agriculture, we are taking agriculturally and environmentally important microorganisms as principal research objects and developing a series of fundamental microbiological studies, aiming to minimize the use of chemical pesticides as well as bio-remediate the polluted fields. Microbial pesticides including bacteria and viruses are ideal alternatives to substitute chemical pesticides. Bacillus thuringiensis (Bt) is a uniquely specific, safe and effective biological insecticide that has been used for more than 50 years. Bt exhibits specific activities against a variety of agricultural pests and is used to produce most of the biopesticides in the market. Whereas B. sphaericus produces active insecticidal proteins specifically against mosquito larvae, thus is widely used as biocontrol agents for disease-transmitting mosquitoes. Viruses from baculoviruses, reoviruses and entomopoxviruses can cause epizootics in the natural insect populations, and they are attractive biological control agents and could be a feasible alternative to chemical pesticides. Forerunners in WIV had developed the first viral insecticide, Helicoverpa armigera nucleopolyhedrovirus (HearNPV) in China, which is also the dominated viral insecticide product in China. On the other hand, chemical pesticides-polluted soil can be bio-remediated by environmental microorganisms since they have evolved into specific metabolic pathways to degrade many chemical pesticides and other man-made pollutants. This requires thorough and detailed studies in specific gene functions, regulations and biotechnologies aiming to its applications. With the solid microbiological research foundation from the past several decades by pioneering microbiologists in WIV such as Dr. Hua-kui Chen and Dr. Hao-ran Jian in the field of Agricultural and Environmental Microbiology, we are not only continuing the research in this traditional research field in WIV but also maketremendous contributions using modern biotechnology to this filed, the institute and the society.
(2) Objectives and scientific significance
This area focuses on the screening of new bacterial or viral strains with insecticidal properties, and the investigation on the functions of specific genes with potentials in biopesticide production. The understanding of the mechanisms of bacterial or viral infections allows the genetic manipulation on specific strains to improve their insecticidal properties. At the same time, efforts are also made in their translational studies in the field application to control pests of agricultural importance. In the field of pollutants biodegradation, we are interested in the functions of genes involved in the pollutant catabolic pathways, their gene organizations and their
regulations. The study focuses on revealing the molecular bases for microbial degradation of pollutants which allow us to understand better how bacteria can degrade chemical pesticides and to construct new catabolic pathways for other chemicals that are not naturally biodegradable. By using genetic manipulation, it also allows the use of bacteria for accumulation of fine chemicals or for maximizing bioremediative processes for pollution control.