Li-Ping Long

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.

Avian-origin H3N2 canine influenza A viruses in Southern China

This study reports four sporadic cases of H3N2 canine influenza in Southern China, which were identified from sick dogs from May 2006 to October 2007. The evolutionary analysis showed that all eight segments of these four viruses are avian-origin and phylogenetically close to the H3N2 canine influenza viruses reported earlier in South Korea. Systematic surveillance is required to monitor the disease and evolutionary behavior of this virus in canine populations in China.

Identification of an H6N6 swine influenza virus in southern China.

This is the first report of avian-like H6N6 swine influenza virus from swine in southern China. Phylogenetic analysis indicated that this virus might originate from domestic ducks. Serological surveillance suggested there had been sporadic H6 swine influenza infections in this area. Continuing study is required to determine if this virus could be established in the swine population and pose potential threats to public health.

Using Sequence Data To Infer the Antigenicity of Influenza Virus

ABSTRACT The efficacy of current influenza vaccines requires a close antigenic match between circulating and vaccine strains. As such, timely identification of emerging influenza virus antigenic variants is central to the success of influenza vaccination programs. Empirical methods to determine influenza virus antigenic properties are time-consuming and mid-throughput and require live viruses. Here, we present a novel, experimentally validated, computational method for determining influenza virus antigenicity on the basis of hemagglutinin (HA) sequence. This method integrates a bootstrapped ridge regression with antigenic mapping to quantify antigenic distances by using influenza HA1 sequences. Our method was applied to H3N2 seasonal influenza viruses and identified the 13 previously recognized H3N2 antigenic clusters and the antigenic drift event of 2009 that led to a change of the H3N2 vaccine strain. IMPORTANCE This report supplies a novel method for quantifying antigenic distance and identifying antigenic variants using sequences alone. This method will be useful in influenza vaccine strain selection by significantly reducing the human labor efforts for serological characterization and will increase the likelihood of correct influenza vaccine candidate selection. This report supplies a novel method for quantifying antigenic distance and identifying antigenic variants using sequences alone. This method will be useful in influenza vaccine strain selection by significantly reducing the human labor efforts for serological characterization and will increase the likelihood of correct influenza vaccine candidate selection.

Identifying antigenicity associated sites in highly pathogenic H5N1 influenza virus hemagglutinin by using sparse learning

Since the isolation of A/goose/Guangdong/1/1996 (H5N1) in farmed geese in southern China, highly pathogenic H5N1 avian influenza viruses have posed a continuous threat to both public and animal health. The non-synonymous mutation of the H5 hemagglutinin (HA) gene has resulted in antigenic drift, leading to difficulties in both clinical diagnosis and vaccine strain selection. Characterizing H5N1s antigenic profiles would help resolve these problems. In this study, a novel sparse learning method was developed to identify antigenicity-associated sites in influenza A viruses on the basis of immunologic data sets (i.e., from hemagglutination inhibition and microneutralization assays) and HA protein sequences. Twenty-one potential antigenicity-associated sites were identified. A total of 17 H5N1 mutants were used to validate the effects of 11 of these predicted sites on H5N1s antigenicity, including 7 newly identified sites not located in reported antibody binding sites. The experimental data confirmed that mutations of these tested sites lead to changes in viral antigenicity, validating our method.

Influenza D virus infection in Mississippi beef cattle.

Abstract A new member of the Orthomyxoviridae family, influenza D virus (IDV), was first reported in swine in the Midwest region of the United States. This study aims to extend our knowledge on the IDV epidemiology and to determine the impact of bovine production systems on virus spread. A total of 15 isolates were recovered from surveillance of bovine herds in Mississippi, and two genetic clades of viruses co-circulated in the same herd. Serologic assessment from neonatal beef cattle showed 94% seropositive, and presumed maternal antibody levels were substantially lower in animals over six months of age. Active IDV transmission was shown to occur at locations where young, weaned, and comingled calves were maintained. Serological characterization of archived sera suggested that IDV has been circulating in the Mississippi cattle populations since at least 2004. Continuous surveillance is needed to monitor the evolution and epidemiology of IDV in the bovine population.

A Perspective on Multiple Waves of Influenza Pandemics

Background A striking characteristic of the past four influenza pandemic outbreaks in the United States has been the multiple waves of infections. However, the mechanisms responsible for the multiple waves of influenza or other acute infectious diseases are uncertain. Understanding these mechanisms could provide knowledge for health authorities to develop and implement prevention and control strategies. Materials and Methods We exhibit five distinct mechanisms, each of which can generate two waves of infections for an acute infectious disease. The first two mechanisms capture changes in virus transmissibility and behavioral changes. The third mechanism involves population heterogeneity (e.g., demography, geography), where each wave spreads through one sub-population. The fourth mechanism is virus mutation which causes delayed susceptibility of individuals. The fifth mechanism is waning immunity. Each mechanism is incorporated into separate mathematical models, and outbreaks are then simulated. We use the models to examine the effects of the initial number of infected individuals (e.g., border control at the beginning of the outbreak) and the timing of and amount of available vaccinations. Results Four models, individually or in any combination, reproduce the two waves of the 2009 H1N1 pandemic in the United States, both qualitatively and quantitatively. One model reproduces the two waves only qualitatively. All models indicate that significantly reducing or delaying the initial numbers of infected individuals would have little impact on the attack rate. Instead, this reduction or delay results in a single wave as opposed to two waves. Furthermore, four of these models also indicate that a vaccination program started earlier than October 2009 (when the H1N1 vaccine was initially distributed) could have eliminated the second wave of infection, while more vaccine available starting in October would not have eliminated the second wave.

Influenza A subtype H3 viruses in feral swine, United States, 2011-2012.

To determine whether, and to what extent, influenza A subtype H3 viruses were present in feral swine in the United States, we conducted serologic and virologic surveillance during October 2011–September 2012. These animals were periodically exposed to and infected with A(H3N2) viruses, suggesting they may threaten human and animal health.

Identification of the source of A (H10N8) virus causing human infection

A novel H10N8 influenza A virus has been detected in three humans in China since December 2013. Although this virus was hypothesized to be a novel reassortant among influenza viruses from wild birds and domestic poultry, its evolutionary path leading to human infection is unknown. Sporadic surveillance at the live poultry market (LPM) suspected to be the source of infection for the first H10N8 patient has shown a gradual increase in influenza virus prevalence culminating with a predominance of H10N8 viruses. Influenza viruses detected in the LPM up to 8 months prior to human infection contributed genetic components to the zoonotic virus. These H10N8 viruses have continued to evolve within this LPM subsequent to the human infection, and continuous assessments of these H10N8 viruses will be necessary. Serological surveillance showed that the virus appears to have been present throughout the LPM system in Nanchang, China. Reduction of the influenza virus burden in LPMs is essential in preventing future emergence of novel influenza viruses with zoonotic and pandemic potential.

Antigenic and Genetic Evolution of Low-Pathogenicity Avian Influenza Viruses of Subtype H7N3 following Heterologous Vaccination

ABSTRACT Outbreaks of low-pathogenicity avian influenza (LPAI) viruses of the H7N3 subtype were first detected in Italy in October 2002, and the virus continued to circulate between 2002 and 2004 in a densely populated poultry area in the northeast portion of that country. This virus circulated in unvaccinated and vaccinated poultry farms, and the infection was controlled in August 2003 by culling, control of movements, improved biosecurity, and heterologous vaccination. In 2004, H7N3 reoccurred in vaccinated poultry farms in which infection had been successfully controlled by the vaccination program. To shed light on this occurrence and the temporal pattern and genetic basis of antigenic drift for avian influenza viruses (AIVs) in the absence and presence of heterologous vaccination, a collection of H7N3 viruses isolated in 2002 and 2004 were characterized genetically and antigenically. Molecular analysis showed that viruses isolated in the 2004 outbreaks after the implementation of vaccination had acquired specific amino acid signatures, most of which were located at reported antibody binding sites of the hemagglutinin (HA) protein. Antigenic characterization of these 2004 isolates showed that they were antigenically different from those isolated prior to the implementation of vaccination. This is the first report on antigenic and genetic evolution of H7 LPAI viruses following the application of heterologous vaccination in poultry. These findings may have an impact on control strategies to combat AI infections in poultry based on vaccination.