Genesis, Evolution and Prevalence of H5N6 Avian Influenza Viruses in China.

Constant surveillance of live poultry markets (LPMs) is currently the best way to predict and identify emerging avian influenza viruses (AIVs) that pose a potential threat to public health. Through surveillance of LPMs from 16 provinces and municipalities in China during 2014-2016, we identified 3,174 AIV-positive samples and isolated and sequenced 1,135 AIVs covering 31 subtypes. Our analysis shows that H5N6 has replaced H5N1 as one of the dominant AIV subtypes in southern China, especially in ducks.

Contribution of intertwined loop to membrane association revealed by Zika virus full-length NS1 structure.

The association of Zika virus (ZIKV) infections with microcephaly and neurological diseases has highlighted an emerging public health concern. Here, we report the crystal structure of the full-length ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis, and immune evasion. Of note, a long intertwined loop is observed in the wing domain of ZIKV NS1, and forms a hydrophobic "spike", which can contribute to cellular membrane association.

Molecular basis of antibody-mediated neutralization and protection against flavivirus.

Antibody-mediated humoral immunity plays a pivotal role in flavivirus control. Neutralizing antibodies targeting viral envelope (E) protein, provide protection against flaviviruses in vivo but can also promote virus infection by antibody-dependent enhancement when antibodies are weakly neutralizing or in subneutralizing concentrations. The molecular basis for antibody-mediated virus neutralization can be revealed by structural studies of monoclonal antibodies complexed with the E protein or virion.

MERS-CoV spike protein: Targets for vaccines and therapeutics.

The disease outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) is still ongoing in the Middle East. Over 1700 people have been infected since it was first reported in September 2012. Despite great efforts, licensed vaccines or therapeutics against MERS-CoV remain unavailable.

Novel avian influenza A (H5N6) viruses isolated in migratory waterfowl before the first human case reported in China, 2014.

In May 2014, China formally confirmed the first human infection with the novel H5N6 avian influenza virus (AIV) in Sichuan Province. Before the first human case was reported, surveillance of AIVs in wild birds resulted in the detection of three H5N6 viruses in faecal samples from migratory waterfowl in Chenhu wetlands, Hubei Province, China. Genetic and phylogenetic analyses revealed that these three novel viruses were closely related to the H5N6 virus that has caused human infections in China since 2014.

Highly pathogenic avian influenza H5N1 Clade 2.3.2.1c virus in migratory birds, 2014-2015.

A novel Clade 2.3.2.

Cyclophilin A protects mice against infection by influenza A virus.

Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.

A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014.

A 73-year-old man was confirmed to have an influenza A (H7N9) virus infection, and the causative agent A/Beijing/02/2014(H7N9) virus was isolated. Genetic and phylogenetic analyses revealed that the virus belonged to a novel genotype, which probably emerged and further reassorted with other H9 or H7 viruses in poultry before transmitting to humans. This virus caused a severe infection with high levels of cytokines and neutralizing antibodies.

The NS1 gene from bat-derived influenza-like virus H17N10 can be rescued in influenza A PR8 backbone.

Influenza A viruses have the potential to cause pandemics due to the introduction of novel subtypes against which human hosts have little or no preexisting immunity. Such viruses may result from reassortment between human and animal influenza viruses. Recently, new influenza-like viruses were identified in bats, raising the concern for a new reservoir of potentially harmful influenza viruses that could form reassortants with categorized human influenza A viruses.

Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody.

Zika virus (ZIKV), a mosquito-borne flavivirus, is a current global public health concern. The flavivirus envelope (E) glycoprotein is responsible for virus entry and represents a major target of neutralizing antibodies for other flaviviruses. Here, we report the structures of ZIKV E protein at 2.

Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses.

The association of Zika virus (ZIKV) infections with microcephaly has resulted in an ongoing public-health emergency. Here we report the crystal structure of a C-terminal fragment of ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune evasion. Comparison with West Nile and dengue virus NS1 structures reveals conserved features but diverse electrostatic characteristics at host-interaction interfaces, thus possibly implying different modes of flavivirus pathogenesis.

Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses.

Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015.

Changes in the Length of the Neuraminidase Stalk Region Impact H7N9 Virulence in Mice.

The neuraminidase stalk of the newly emerged H7N9 influenza virus possesses a 5-amino-acid deletion. This study focuses on characterizing the biological functions of H7N9 with varied neuraminidase stalk lengths. Results indicate that the 5-amino-acid deletion had no impact on virus infectivity or replication in vitro or in vivo compared to that of a virus with a full-length stalk, but enhanced virulence in mice was observed for H7N9 encoding a 19- to 20-amino-acid deletion, suggesting that N9 stalk length impacts virulence in mammals, as N1 stalk length does.

Deep sequencing reveals the viral adaptation process of environment-derived H10N8 in mice.

The H10N8 virus was isolated from the water of Dongting Lake, China. Mice were infected while showing no obvious symptoms and replication was restricted to the lungs. When the wild-type virus was serially passaged in the lungs of mice, the resulting viruses became lethal and capable of replication in many other organs.

MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease.

Super-spreading occurs when a single patient infects a disproportionate number of contacts. The 2015 MERS-CoV, 2003 SARS-CoV, and to a lesser extent 2014-15 Ebola virus outbreaks were driven by super-spreaders. We summarize documented super-spreading in these outbreaks, explore contributing factors, and suggest studies to better understand super-spreading.

NK-cells are involved in thymic atrophy induced by influenza A virus infection.

NK-cells have traditionally been viewed as innate effector lymphocytes that serve as a first line of defence against a range of viruses and tumours. More recently, the importance of NK-cell immunoregulatory functions has been highlighted. NK-cells can inhibit antiviral T-cell responses, and also play an important role in controlling harmful T-cell activity in autoimmunity and transplantation settings.

Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015.

Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.

Epidemiology, Evolution, and Recent Outbreaks of Avian Influenza Virus in China.

Novel reassortants of H7N9, H10N8, and H5N6 avian influenza viruses (AIVs) are currently circulating in China's poultry flocks, occasionally infecting humans and other mammals. Combined with the sometimes enzootic H5N1 and H9N2 strains, this cauldron of genetically diverse AIVs pose significant risks to public health. Here, we review the epidemiology, evolution, and recent outbreaks of AIVs in China, discuss reasons behind the recent increase in the emergence of novel AIVs, and identify warning signs which may point to the emergence of a potentially virulent and highly transmissible AIV to humans.

Two novel reassortants of avian influenza A (H5N6) virus in China.

Eight avian influenza A (H5N6) viruses were isolated from live poultry markets (LPMs) in Sichuan and Jiangxi Provinces in China in 2014, including those close to the county where the human H5N6 infection occurred. Genetic and phylogenetic analyses revealed that these H5N6 viruses were novel reassortants between H5N1 clade 2.3.