High Prevalence and Genetic Diversity of HCV among HIV-1 Infected People from Various High-Risk Groups in China

BACKGROUND: Co-infection with HIV-1 and HCV is a significant global public health problem and a major consideration for anti-HIV-1 treatment. HCV infection among HIV-1 positive people who are eligible for the newly launched nationwide anti-HIV-1 treatment program in China has not been well characterized. METHODOLOGY: A nationwide survey of HIV-1 positive injection drug uses (IDU), former paid blood donors (FBD), and sexually transmitted cases from multiple provinces including the four most affected provinces in China was conducted. HCV prevalence and genetic diversity were determined. We found that IDU and FBD have extremely high rates of HCV infection (97% and 93%, respectively). Surprisingly, people who acquired HIV-1 through sexual contact also had a higher rate of HCV infection (20%) than the general population. HIV-1 subtype and HCV genotypes were amazingly similar among FBD from multiple provinces stretching from Central to Northeast China. However, although patterns of overland trafficking of heroin and distinct HIV-1 subtypes could be detected among IDU, HCV genotypes of IDU were more diverse and exhibited significant regional differences. CONCLUSION: Emerging HIV-1 and HCV co-infection and possible sexual transmission of HCV in China require urgent prevention measures and should be taken into consideration in the nationwide antiretroviral treatment program

Mechanism of 150-cavity formation in influenza neuraminidase

The recently discovered 150-cavity in the active site of group-1 influenza A neuraminidase (NA) proteins provides a target for rational structure-based drug development to counter the increasing frequency of antiviral resistance in influenza. Surprisingly, the 2009 H1N1 pandemic virus (09N1) neuramidase was crystalized without the 150-cavity characteristic of group-1 NAs. Here we demonstrate, through a total sum of 1.6 μs of biophysical simulations, that 09N1 NA exists in solution preferentially with an open 150-cavity. Comparison with simulations using avian N1, human N2 and 09N1 with a I149V mutation and an extensive bioinformatics analysis suggests that the conservation of a key salt bridge is crucial in the stabilization of the 150-cavity across both subtypes. This result provides an atomic-level structural understanding of the recent finding that antiviral compounds designed to take advantage of contacts in the 150-cavity can inactivate both 2009 H1N1 pandemic and avian H5N1 viruses

Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus : studies in the pig model of influenza

Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs

Longitudinal molecular microbial analysis of influenza-like illness in New York City, may 2009 through may 2010

<p>Abstract</p> <p>Background</p> <p>We performed a longitudinal study of viral etiology in samples collected in New York City during May 2009 to May 2010 from outpatients with fever or respiratory disease symptoms in the context of a pilot respiratory virus surveillance system.</p> <p>Methods</p> <p>Samples were assessed for the presence of 13 viruses, including influenza A virus, by MassTag PCR.</p> <p>Results</p> <p>At least one virus was detected in 52% of 940 samples analyzed, with 3% showing co-infections. The most frequently detected agents were rhinoviruses and influenza A, all representing the 2009 pandemic H1N1 strain. The incidence of influenza H1N1-positive samples was highest in late spring 2009, followed by a decline in summer and early fall, when rhinovirus infections became predominant before H1N1 reemerged in winter. Our study also identified a focal outbreak of enterovirus 68 in the early fall of 2009.</p> <p>Conclusion</p> <p>MassTag multiplex PCR affords opportunities to track the epidemiology of infectious diseases and may guide clinicians and public health practitioners in influenza-like illness and outbreak management. Nonetheless, a substantial proportion of influenza-like illness remains unexplained underscoring the need for additional platforms.</p

The month of July: an early experience with pandemic influenza A (H1N1) in adults with cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Pandemic Influenza A (H1N1) 2009 is a novel viral infection that emerged in March 2009. This is the first report addressing the clinical course of patients with cystic fibrosis (CF) and H1N1 infection.</p> <p>Methods</p> <p>All patients with an influenza-like illness (ILI) attending our adult centre during July 2009 were identified. Baseline respiratory function, nutritional status, approach to management and short-term clinical course were recorded.</p> <p>Results</p> <p>Most patients experienced a mild course and were able to be managed with antiviral agents as an outpatient. Robust infection control policies were implemented to limit transmission of H1N1 infection within our CF centre. Patients with severe lung disease, poor baseline nutritional reserve and presenting with more than 48 hours of ILI experienced a more severe course. Prompt antiviral therapy within the first 48 hours of illness may have been important in improving outcomes.</p> <p>Conclusions</p> <p>This observational study demonstrates that most adults with CF with H1N1 infection had mild clinical courses and recovered rapidly.</p

Rapid Detection and Subtyping of Human Influenza A Viruses and Reassortants by Pyrosequencing

Background: Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. Methodology/Principal Findings: A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. Conclusions/Significance: In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is mor

HCV 6a Prevalence in Guangdong Province Had the Origin from Vietnam and Recent Dissemination to Other Regions of China: Phylogeographic Analyses

Recently in China, HCV 6a infection has shown a fast increase among patients and blood donors, possibly due to IDU linked transmission.We recruited 210 drug users in Shanwei city, Guangdong province. Among them, HCV RNA was detected in 150 (71.4%), both E1 and NS5B genes were sequenced in 136, and 6a genotyped in 70. Of the 6a sequences, most were grouped into three clusters while 23% represent emerging strains. For coalescent analysis, additional 6a sequences were determined among 21 blood donors from Vietnam, 22 donors from 12 provinces of China, and 36 IDUs from Liuzhou City in Guangxi Province. Phylogeographic analyses indicated that Vietnam could be the origin of 6a in China. The Guangxi Province, which borders Vietnam, could be the first region to accept 6a for circulation. Migration from Yunnan, which also borders Vietnam, might be equally important, but it was only detected among IDUs in limited regions. From Guangxi, 6a could have further spread to Guangdong, Yunnan, Hainan, and Hubei provinces. However, evidence showed that only in Guangdong has 6a become a local epidemic, making Guangdong the second source region to disseminate 6a to the other 12 provinces. With a rate of 2.737×10⁻³ (95% CI: 1.792×10⁻³ to 3.745×10⁻³), a Bayesian Skyline Plot was portrayed. It revealed an exponential 6a growth during 1994-1998, while before and after 1994-1998 slow 6a growths were maintained. Concurrently, 1994-1998 corresponded to a period when contaminated blood transfusion was common, which caused many people being infected with HIV and HCV, until the Chinese government outlawed the use of paid blood donations in 1998.With an origin from Vietnam, 6a has become a local epidemic in Guangdong Province, where an increasing prevalence has subsequently led to 6a spread to many other regions of China

Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread

Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence.Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins.We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics

Genomic Signature-Based Identification of Influenza A Viruses Using RT-PCR/Electro-Spray Ionization Mass Spectrometry (ESI-MS) Technology

BACKGROUND: The emergence and rapid spread of the 2009 H1N1 pandemic influenza A virus (H1N1pdm) in humans highlights the importance of enhancing the capability of existing influenza surveillance systems with tools for rapid identification of emerging and re-emerging viruses. One of the new approaches is the RT-PCR electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology, which is based on analysis of base composition (BC) of RT-PCR amplicons from influenza "core" genes. Combination of the BC signatures represents a "genomic print" of an influenza A virus. METHODOLOGY/PRINCIPAL FINDINGS: Here, 757 samples collected between 2006 and 2009 were tested, including 302 seasonal H1N1, 171 H3N2, 7 swine triple reassortants, and 277 H1N1pdm viruses. Of the 277 H1N1pdm samples, 209 were clinical specimens (throat, nasal and nasopharyngeal swabs, nasal washes, blood and sputum). BC signatures for the clinical specimen from one of the first cases of the 2009 pandemic, A/California/04/2009, confirmed it as an unusual, previously unrecognized influenza A virus, with "core" genes related to viruses of avian, human and swine origins. Subsequent analysis of additional 276 H1N1pdm samples revealed that they shared the genomic print of A/California/04/2009, which differed from those of North American swine triple reassortant viruses, seasonal H1N1 and H3N2 and other viruses tested. Moreover, this assay allowed distinction between "core" genes of co-circulating groups of seasonal H1N1, such as clades 2B, 2C, and their reassortants with dual antiviral resistance to adamantanes and oseltamivir. CONCLUSIONS/SIGNIFICANCE: The RT-PCR/ESI-MS assay is a broad range influenza identification tool that can be used directly on clinical specimens for rapid and accurate detection of influenza virus genes. The assay differentiates the H1N1pdm from seasonal and other nonhuman hosts viruses. Although not a diagnostic tool, this assay demonstrates its usefulness and robustness in influenza virus surveillance and detection of novel and unusual viruses with previously unseen genomic prints

Climate Change Alters Seedling Emergence and Establishment in an Old-Field Ecosystem

Background: Ecological succession drives large-scale changes in ecosystem composition over time, but the mechanisms whereby climatic change might alter succession remain unresolved. Here, we asked if the effects of atmospheric and climatic change would alter tree seedling emergence and establishment in an old-field ecosystem, recognizing that small shifts in rates of seedling emergence and establishment of different species may have long-term repercussions on the transition of fields to forests in the future. Methodology/Principal Findings: We introduced seeds from three early successional tree species into constructed old-field plant communities that had been subjected for 4 years to altered temperature, precipitation, and atmospheric CO 2 regimes in an experimental facility. Our experiment revealed that different combinations of atmospheric CO2 concentration, air temperature, and soil moisture altered seedling emergence and establishment. Treatments directly and indirectly affected soil moisture, which was the best predictor of seedling establishment, though treatment effects differed among species. Conclusions: The observed impacts, coupled with variations in the timing of seed arrival, are demonstrated as predictors o