Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; Houttuynia ; chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Inflammation ; drug therapy ; pathology ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Intestinal Mucosa ; drug effects ; metabolism ; microbiology ; pathology ; Lung ; drug effects ; metabolism ; pathology ; Male ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; pathology ; physiopathology ; Plant Extracts ; chemistry ; Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Toll-Like Receptors ; metabolism ; Zonula Occludens-1 Protein ; metabolism

BACKGROUNDThe aim of this research was to evaluate long-term pulmonary sequelae on paired inspiration-expiration thin-section computed tomography (CT) scans 3 years after influenza A (H1N1) virus-associated pneumonia, and to analyze the affecting factors on pulmonary fibrosis.

METHODSTwenty-four patients hospitalized with H1N1 virus-associated pneumonia at our hospital between September 2009 and January 2010 were included. The patients underwent thin-section CT 3 years after recovery. Abnormal pulmonary lesion patterns (ground-glass opacity, consolidation, parenchymal bands, air trapping, and reticulation) and evidence of fibrosis (architectural distortion, traction bronchiectasis, or honeycombing) were evaluated on follow-up thin-section CT. Patients were assigned to Group 1 (with CT evidence of fibrosis) and Group 2 (without CT evidence of fibrosis). Demographics, rate of mechanical ventilation therapy, rate of intensive care unit admission, cumulative prednisolone-equivalent dose, laboratory tests results (maximum levels of alanine aminotransferase, aspartate transaminase [AST], lactate dehydrogenase [LDH], and creatine kinase [CK]), and peak radiographic opacification of 24 patients during the course of their illness in the hospital were compared between two groups.

RESULTSParenchymal abnormality was present in 17 of 24 (70.8%) patients and fibrosis occurred in 10 of 24 (41.7%) patients. Patients in Group 1 (10/24; 41.7%) had a higher rate of mechanical ventilation therapy (Z = -2.340, P = 0.019), higher number of doses of cumulative prednisolone-equivalent (Z = -2.579, P = 0.010), higher maximum level of laboratory tests results (AST [Z = -2.140, P = 0.032], LDH [Z = -3.227, P = 0.001], and CK [Z = -3.345, P = 0.019]), and higher peak opacification on chest radiographs (Z = -2.743, P = 0.006) than patients in group 2 (14/24; 58.3%).

CONCLUSIONSH1N1 virus-associated pneumonia frequently is followed by long-term pulmonary sequelae, including fibrotic changes, in lung parenchyma. Patients who need more steroid therapy, need more mechanical ventilation therapy, had higher laboratory tests results (maximum levels of AST, LDH, and CK), and had higher peak opacification on chest radiographs during treatment are more likely to develop lung fibrosis.

Adult ; Female ; Humans ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Influenza, Human ; complications ; virology ; Lung ; diagnostic imaging ; pathology ; virology ; Male ; Middle Aged ; Pneumonia ; complications ; diagnostic imaging ; microbiology ; Tomography, X-Ray Computed ; methods

BACKGROUNDSome research groups have hypothesized that human rhinoviruses (HRVs) delayed the circulation of the 2009 pandemic influenza A(H1N1) virus (A(H1N1)pdm09) at the beginning of Autumn 2009 in France. This study aimed to evaluate the relationship between HRV and A(H1N1)pdm09 in pediatric patients with influenza-like illness in Beijing, China.

METHODSA systematic analysis to detect A(H1N1)pdm09 and seasonal influenza A virus (FLU A) was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1, 2009 to February 28, 2010, while a one-step real-time RT-PCR (rRT-PCR) assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.

RESULTSDuring the survey period, only one wave of A(H1N1)pdm09 was observed. The percentage of positive cases for A(H1N1)pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010. Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September (2.2%) and October (3.3%), revealing that the peak of HRV infection in 2009 was similar to that of other years. Among the 1 146 specimens examined for HRVs, 21 (1.8%) were HRV-positive, which was significantly lower than that reported previously in Beijing (15.4% to 19.2%) (P < 0.01). Overall, 6 samples were positive for both A(H1N1)pdm09 and HRV, which represented a positive relative frequency of 1.60% and 2.08% HRV, considering the A(H1N1)pdm09-positive and -negative specimens, respectively. The odds ratio was 0.87 (95% CI 0.32; 2.44, P = 0.80).

CONCLUSIONSHRVs and A (H1N1)pdm09 co-circulated in this Chinese population during September and October 2009, and the HRV epidemic in 2009 did not affect A(H1N1)pdm09 infection rates in Beijing, China as suggested by other studies. However, the presence of A(H1N1)pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.

Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Influenza, Human ; epidemiology ; Male ; Picornaviridae Infections ; epidemiology ; Rhinovirus ; pathogenicity

This study aims to investigate the virological impact of the stalk region and cysteine (C) in neuraminidase (NA) of influenza A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1) viruses. The NA of A/ Anhui/1/05 (H5N1), defined as AH N1, lacked 20 amino acids (including C, defined as s20) as compared with NA of A/Ohio/07/2009 (H1N1) (defined as 09N1). We deleted s20 of 09N1 to construct 09N1-s20, and inserted s20 into AH N1 to construct AH N1+s20. To investigate the impact of C on the biological function of NA, we deleted C in 09N1 to construct 09N1-C and inserted C into AH N1 to construct AH N1-C. The pseudo-type viral particle (pp) system was used to evaluate the impact of these mutants on virology. The combination of 09N1-C and 09H1 (defined as 09H1::09N1-C) showed an infectivity 8 times that of the wild type 09H1::09N1, while the infectivity of the combination of AH N1+C and AH H5 (defined as AH H5::AH N1+C) was much lower than that of the wild type AH H5::AH N1. The infectivity of the combination of 09N1-s20 and 09H1 (defined as 09H1::09N1-s20) was 4 times that of the wild type 09H1::09N1; the infectivity of the combination of AH N1+s20 and AH H5 (defined as AH H5:: AH N1+s20) was 1/7 that of the wild type AH H5::AH N1. The co-existence of 09N1-C and AH H5 displayed 6 times the infectivity of AH H5::09N1, while the infectivity of 09H1::AH N1+C was very low. Multimer analysis showed that in the wild type 09N1, the forms of NA were dimer > tetramer > monomer; the major component of NA in 09N1-C was monomer; in 09N1-s20, the forms of NA were monomer > dimer. AH N1 was mainly composed of monomer; in AH N1+s20, the forms of NA were dimer > monomer > tetramer; in AH N1+C, the forms of NA were dimer > tetramer. Deletion of C or s20 from 09N1 did not change the expression of NA. The study suggested that deletion of C from the stalk region of NA in A/Ohio/07/2009 (H1N1) increases infectivity. Insertion of C into NA's stalk region of A/ Anhui/1/05 (H5N1) significantly decreases infectivity. Cysteine deletion in the stalk region is important for the infectivity of A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1). It may interfere with the infectivity via changes in NA polymerization.
Amino Acid Motifs ; Humans ; Influenza A Virus, H1N1 Subtype ; chemistry ; enzymology ; genetics ; pathogenicity ; Influenza A Virus, H5N1 Subtype ; chemistry ; enzymology ; genetics ; pathogenicity ; Influenza, Human ; virology ; Neuraminidase ; chemistry ; genetics ; metabolism ; Viral Proteins ; chemistry ; genetics ; metabolism ; Virulence

PURPOSE: Pneumonia was an important cause of death in 2009 H1N1 influenza pandemic (pH1N1). Clinical characteristics of pH1N1 have been described well, but discriminative characteristics suggesting pH1N1 infection in pneumonia patients are not evident today. We evaluated differences between clinical and radiologic characteristics for those associated and not associated with pH1N1 influenza during the pandemic period. MATERIALS AND METHODS: We reviewed all patients with pneumonia who visited the Armed Forces Capital Hospital between July 2009 and February 2010. During this period, all pneumonia patients were tested for pH1N1 by reverse transcription-polymerase chain reaction (RT-PCR) using nasopharyngeal specimens. RESULTS: In total, 98 patients with pneumonia were enrolled. Their median age was 20 years and all patients were males. Forty-nine (50%) of patients had pH1N1 infection and the others (50%) had negative results in pH1N1 RT-PCR. Patients with pH1N1 infection complained of dyspnea more commonly (83.3% vs. 29.0%; p<0.001), had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores [5 (range, 0-12) vs. 3 (range, 0-11); p<0.01], fewer days of prehospital illness [2 (range, 0-10) vs. 4 (range, 0-14); p=0.001], and a higher chance of bilateral infiltrates on chest X-ray (CXR) (67.3% vs. 14.3%; p<0.001) and ground-glass opacity (GGO) lesions on computed tomography (CT; 48.9% vs. 22.0%; p<0.001) than patients without pH1N1 infection. CONCLUSION: Dyspnea, bilateral infiltrates on CXR, and GGO on CT were dominant features in pH1N1-associated pneumonia. Understanding these characteristics can help selection of patients who require prompt antiviral therapy.
Adolescent ; Adult ; Antiviral Agents/therapeutic use ; Dyspnea/virology ; Humans ; Influenza A Virus, H1N1 Subtype/genetics/*pathogenicity ; Influenza, Human/*complications/radiography/virology ; Male ; Middle Aged ; Pneumonia/etiology/radiography ; Pneumonia, Viral/drug therapy/etiology/*radiography/*virology ; Radiography, Thoracic ; Tomography, X-Ray Computed ; Young Adult

Adult ; Female ; Follow-Up Studies ; Humans ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Influenza, Human ; diagnosis ; Pregnancy ; Respiratory Distress Syndrome, Adult ; diagnosis ; virology

The use of antiviral drugs such as influenza neuraminidase (NA) inhibitors is a critical strategy to prevent and control flu pandemic, but this strategy faces the challenge of emerging drug-resistant strains. For a highly pathogenic avian influenza (HPAI) H5N1 virus, biosafety restrictions have significantly limited the efforts to monitor its drug responses and mechanisms involved. In this study, a rapid and biosafe assay based on NA pseudovirus was developed to study the resistance of HPAI H5N1 virus to NA inhibitor drugs. The H5N1 NA pseudovirus was comprehensively tested using oseltamivir-sensitive strains and their resistant mutants. Results were consistent with those in previous studies, in which live H5N1 viruses were used. Several oseltamivir-resistant mutations reported in human H1N1 were also identified to cause decreased oseltamivir sensitivity in H5N1 NA by using the H5N1 NA pseudovirus. Thus, H5N1 NA pseudoviruses could be used to monitor HPAI H5N1 drug resistance rapidly and safely.
Animals ; Birds ; Drug Resistance, Viral ; genetics ; Enzyme Inhibitors ; therapeutic use ; HEK293 Cells ; Humans ; Influenza A Virus, H1N1 Subtype ; drug effects ; genetics ; pathogenicity ; Influenza A Virus, H5N1 Subtype ; drug effects ; genetics ; pathogenicity ; Influenza in Birds ; drug therapy ; genetics ; virology ; Influenza, Human ; drug therapy ; genetics ; virology ; Mutagenesis, Site-Directed ; Neuraminidase ; antagonists & inhibitors ; genetics ; Oseltamivir ; administration & dosage

BACKGROUNDThe global outbreak of influenza A (H1N1) has led to the Ministry of Health of China listing it as one of the A-class infectious diseases. Pneumonia is the most serious complication of influenza A, commonly causing death. Populations are ordinarily susceptible to influenza A. This study aimed to investigate the imaging manifestation features of critical influenza A (H1N1) pneumonia and to improve its diagnostic techniques.

METHODSA total of seven death cases from critical influenza A (H1N1) pneumonia were retrospectively analyzed on their imaging manifestations and autopsy data. Pulmonary CT scanning was performed for five cases, with one receiving additional chest X-ray and chest CT scanning, and chest postero-anterior position X-ray examination was performed for other two. Autopsy was performed for five cases and postmortem examinations were performed for other two cases.

RESULTSThe seven cases of influenza A showed critical manifestations in 4 - 7 days after symptoms onset, with two having basic diseases of diabetes and one being pregnant. Extensive blurry high-density shadows of bilateral lungs were found in three cases, which were most obvious in middle and inferior parts of lungs. Pulmonary CT scanning revealed bilateral flaky parenchymal shadows in peripheral, dorsal and fundus segments of the middle-inferior parts of lungs, with one case of complicated pneumothorax, atelectasis and pleural effusion and another case of thin-walled cavity and dilated bronchi shadows in the superior parts of lungs.

CONCLUSIONSDiagnostic imaging is an important assessing tool for critical influenza A (H1N1) pneumonia. The imaging manifestations are characteristic instead of being specific. The definitive diagnosis can be made in combination with clinical examinations and laboratory tests.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Influenza, Human ; diagnosis ; diagnostic imaging ; virology ; Male ; Middle Aged ; Pregnancy ; Radiography ; Retrospective Studies ; Young Adult

Since March 2009, pandemic A/H1N1/2009 influenza virus has been spreading throughout many countries including China. The emerged virus caused great harm to human health and social economy. Hemagglutinin (HA) is the most important viral surface glycoprotein, mainly possessing three kinds of functions: (1) binding to host cell receptor, (2) triggering the fusion between viral envelop and target cell membrane, (3) stimulating the body to generate the neutralizing antibody. Advances in the structure, primary function, evolution and antigenicity of pandemic A/H1N1/2009 influenza virus HA protein are reviewed in this paper.
Animals ; Evolution, Molecular ; Hemagglutinin Glycoproteins, Influenza Virus ; chemistry ; genetics ; immunology ; metabolism ; Humans ; Influenza A Virus, H1N1 Subtype ; genetics ; immunology ; pathogenicity ; physiology ; Influenza, Human ; epidemiology ; virology ; Pandemics

BACKGROUND/AIMS: Pandemic influenza A (H1N1) virus infection presents with variable severity. However, little is known about clinical predictors of disease severity. We studied the clinical predictors of severe pandemic H1N1 pneumonia and their correlation with radiological findings. METHODS: We reviewed medical and radiological records of adults with pandemic H1N1 pneumonia. After classification of patients into severe and non-severe groups, the following data were evaluated: demographic data, pneumonia severity index (PSI), CURB65, risk factors, time to first dose of antiviral medication, routine laboratory data, clinical outcome, and radiological characteristics. RESULTS: Of 37 patients with pandemic H1N1 pneumonia, 12 and 25 were assigned to the severe and non-severe groups, respectively. PSI score, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dyhydrogenase (LDH) levels were higher in the severe group than in the non-severe group (p = 0.035, 0.0003, 0.0023, and 0.0002, respectively). AST, ALT, and LDH levels were positively correlated with the radiological findings (p < 0.0001, 0.0003, and < 0.0001, respectively) and with the number of involved lobes (p = 0.663, 0.0134, and 0.0019, respectively). The most common finding on high resolution computed tomography (HRCT) scans was ground-glass attenuation with consolidation (n = 22, 60%), which had a predominantly patchy distribution (n = 31). CONCLUSIONS: We demonstrated a positive correlation between clinical findings, such as serum AST, ALT, and LDH levels, and radiological findings. A combination of clinical and HRCT indicators would be useful in predicting the clinical outcome of pandemic H1N1 pneumonia.
Adolescent ; Adult ; Aged ; Alanine Transaminase/blood ; Antiviral Agents/therapeutic use ; Aspartate Aminotransferases/blood ; Biological Markers/blood ; Chi-Square Distribution ; Clinical Enzyme Tests ; Female ; Humans ; Influenza A Virus, H1N1 Subtype/*pathogenicity ; Influenza, Human/*diagnosis/mortality/radiography/therapy/virology ; L-Lactate Dehydrogenase/blood ; Lung/*radiography/virology ; Male ; Middle Aged ; *Pandemics ; Pneumonia, Viral/*diagnosis/mortality/radiography/therapy/virology ; Predictive Value of Tests ; Prognosis ; Republic of Korea/epidemiology ; Respiration, Artificial ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; *Tomography, X-Ray Computed ; Young Adult