Distribution of Avian Influenza A Viruses in Poultry-Related Environment and Its Association with Human Infection in Henan, 2016 to 2017

Objective To survey avian influenza A viruses(AIVs) in the environment and explore the reasons for the surge in human H7 N9 cases.Methods A total of 1,045 samples were collected from routine surveillance on poultry-related environments and 307 samples from human H7 N9 cases-exposed environments in Henan from 2016 to2017. The nucleic acids of influenza A(Flu A), H5, H7, and H9 subtypes were detected by real-time polymerase chain reaction.Results A total of 27 H7 N9 cases were confirmed in Henan from 2016 to 2017, 24 had a history of live poultry exposure, and 15 had H7 N9 virus detected in the related live poultry markets(LPMs). About 96%(264/275) Flu A positive-environmental samples were from LPMs. H9 was the main AIV subtype(10.05%) from routine surveillance sites with only 1 H7-positive sample, whereas 21.17% samples were H7-positive in H7 N9 cases-exposed environments. Samples from H7 N9 cases-exposed LPMs(47.56%)had much higher AIVs positive rates than those from routine surveillance sites(12.34%). The H7+H9 combination of mixed infection was 78.18%(43/55) of H7-positive samples and 41.34%(43/104) of H9-positive samples.Conclusion The contamination status of AIVs in poultry-related environments is closely associated with the incidence of human infection caused by AIVs. Therefore, systematic surveillance of AIVs in LPMs in China is essential for the detection of novel reassortant viruses and their potential for interspecies transmission.

Prevalence of transfusion transmissible infections among various donor groups:A comparative analysis

BACKGROUND Transfusion transmissible infections(TTIs)are illnesses spread through contaminated blood or blood products.In India,screening for TTIs such as hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency virus(HIV)-I/II,malaria,and syphilis is mandatory before blood transfusions.Worldwide,HCV,HBV,and HIV are the leading viruses causing mortality,affecting millions of people globally,including those with co-infections of HIV/HCV and HIV/HBV.Studies highlight the impact of TTIs on life expectancy and health risks,such as liver cirrhosis,cancer,and other diseases in individuals with chronic HBV.Globally,millions of blood donations take place annually,emphasizing the importance of maintaining blood safety.AIM To study the prevalence of TTIs,viz.,HBV,HCV,HIV I/II,syphilis,and malaria parasite(MP),among different blood donor groups.METHODS The study assessed the prevalence of TTIs among different blood donor groups in Delhi,India.Groups included total donors,in-house donors,total camp donors,institutional camp donors,and community camp donors.Tests for HIV,HBV,and HCV were done using enzyme-linked immunosorbent assay,while syphilis was tested with rapid plasma reagins and MP rapid card methods.The prevalence of HBV,HCV,HIV,and syphilis,expressed as percentages.Differences in infection rates between the groups were analyzed usingχ²tests and P-values(less than 0.05).RESULTS The study evaluated TTIs among 42158 blood donors in Delhi.The overall cumulative frequency of TTIs in total blood donors was 2.071%,and the frequencies of HBV,HCV,HIV-I/II,venereal disease research laboratory,and MP were 1.048%,0.425%,0.221%,0.377%,and 0.0024%,respectively.In-house donors,representing 37656 donors,had the highest transfusion transmissible infection(TTI)prevalence at 2.167%.Among total camp donors(4502 donors),TTIs were identified in 1.266%of donors,while community camp donors(2439 donors)exhibited a prevalence of 1.558%.Institutional camp donors(2063 donors)had the lowest TTI prevalence at 0.921%.Statistical analysis revealed significant differences in overall TTI prevalence,with total and in-house donors exhibiting higher rates compared to camp donors.CONCLUSION Ongoing monitoring and effective screening programs are essential for minimizing TTIs.Customizing blood safety measures for different donor groups and studying socio-economic-health factors is essential to improving blood safety.

H5N1 influenza viruses： outbreaks and biological properties

All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties.

HLA class Ⅱ associated with outcomes of hepatitis B and C infections

Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered one of the most important host factors with respect to outcomes.To date,conventional genotyping studies have shown that HLA classⅡloci are mainly associated with spontaneous clearance of HBV and HCV.However,the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear.A recent genome-wide association study(GWAS)using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms(SNPs)associated with the outcomes of hepatitis virus infection.Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLADPB1 loci are associated with persistent HBV infection in Asian populations.To date,however,few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA.There are not enough studies to reveal the function of HLA-DP.GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis,hepatic fibrosis,and the development of hepatocellular carcinoma.The results of one cohort were not always consistent with those of other cohorts.To solve several controversial issues,it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

Multiplication of the Recombinant Strain Re-7 of Avian Influenza Virus Subtype H5 in MDCK Cells

This study was conducted to explore the multiplication pattern of the recombinant strain Re-7 of avian influenza virus subtype H5 in Madin Darby Canine Kidney （MDCK） cells and to determine the optimal multiplicity of infection （MOI） and the optimal time for virus harvest. The recombinant strain Re-7 was inoculated at different MOIs into MDCK cells grown in serum-free medium in 100 L bioreactors for replication. Then, the hemagglutination（HA） titer, 50% tissue culture infectious dose （TCID50） and 50% embryo infectious dose （EID50） of culture medium were measured once every 12 h from 24 h after virus inoculation to determine the optimal MOI. After that, virus was inoculated at the optimal MOI determined above into MDCK cells for large-scale virus replication to determine the optimal time for virus harvest. The results showed that the optimal MOI was 10 2, and the optimal time for virus harvest was 60 h after inoculation. Under these conditions, the HA titer, TCIDso per 1 mL and EIDso per 0.1 mL were increased to 1：102 4, 10^7.33 and 10^6.83, respectively. This study provides relatively stable parameters for large-scale production of the recombinant strain Re-7 of avian influenza virus subtype H5.

Successful High-Dosage Dexamethasone Treatment of H1N1 Influenza A Pneumonia Complicated with Acute Necrotizing Encephalitis in an HIV-Infected Adult

Neurological manifestations in H1N1 influenza A infection are very rare, especially in adults, and its mechanism of action is still uncertain. Here, we reported the case of a 53-year-old woman with human immunodeficiency virus infection (HIV) who had H1N1 influenza A pneumonia complicated with very rare acute necrotizing encephalitis, although the HIV was under control. With prompt identification and administration of high dosage of dexamethasone, her mental status improved from stupor to clear, with minimal right hemiparesis. Further, brain magnetic resonance image revealed great resolution of mass effect. This dramatic improvement in response to the treatment may improve our understanding of the pathophysiology between H1N1 influenza A infection and acute necrotizing encephalitis.

Insights into gastrointestinal manifestation of human immunodeficiency virus:A narrative review

Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.

Bilateral Peripheral Facial Paralysis Combined with HIV Meningitis During Acute HIV-1 Infection: A Case Report

Here we reported a Chinese case of bilateral peripheral facial paralysis(PFP) in human immunodeficiency virusc(HIV) infected population. A 38-year-old homosexual male patient was referred to our hospital for bilateral facial paralysis. 21 days prior to admission he had developed high fever, chills, headache, fatigue, general malaise, nausea and vomiting. Neurological examination revealed bilateral ptosis of lower lip and cheeks, as well as failure of bilateral eyes closure. Analysis of cerebrospinal fluid(CSF) revealed pleocytosis, a marked rise of micro total protein and a marked rise of intrathecal lgG synthesis. The result of HIV-1 serology was positive by ELISA and that was confirmed by western blot. His CD4^+ cell count was 180 cells/mm^3. HIV-1 viral load in CSF was almost 10 times higher than that in plasma. The patient's condition improved steadily and experienced complete resolution of bilateral PFP after 2 months.

Significant increase in HBV, HCV, HIV and syphilis infections among blood donors in West Bengal, Eastern India 2004-2005: Exploratory screening reveals high frequency of occult HBV infection

AIM: To evaluate the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kolkata, Eastern India for two consecutive years and to conduct a pilot study to explore the presence of HBV DNA among hepatitis B surface antigen (HBsAg) negative but anti-HBc positive blood donors. METHODS: Seroprevalence of HBsAg, anti-HCV and anti-HIV was studied among 113 051 and 106 695 voluntary blood donors screened in 2004 and 2005, respectively. Moreover, a pilot study on 1027 HBsAg negative donors was carried out for evaluating the presence of HBV DNA by PCR on HBsAg negative/anti- HBc positive donors. RESULTS: A statistically significant increase in the prevalence of HBV (1448 vs 1768, P < 0.001), HIV (262 vs 374, P < 0.001), HCV (314 vs 372, P = 0.003) and syphilis (772 vs 853, P = 0.001) infections was noted among blood donors of Kolkata West Bengal in 2005 as compared to 2004. Moreover, the exploratory study on 1027 HBsAg negative donors revealed that 188 (18.3%)of them were anti-HBc positive out of which 21% were positive for HBV DNA. CONCLUSION: The findings of this study underscore the significantly increasing endemicity of hepatitis viruses, syphilis and HIV among the voluntary blood donors of our community. The pilot study indicates a high rate of prevalence of HBV DNA among HBsAg negative/anti-HBc positive donors and thus emphasizes the need for a more sensitive and stringent screening algorithm for blood donations.

TT virus infection in patients with chronic hepatitis B and response of TTV to lamivudine

AIM: To investigate the responses of TT virus (TTV) and hepatitis B virus (HBV) to a long-term lamivudine therapy.METHODS: Sixteen patients infected with both TTV and HBV were treated with lamivudine 100 mg daily for 30 months. Blood samples were drawn at the beginning of the therapy and subsequently at month 3, 6, 9, 12 and 30.Serum TTV was quantified by real time PCR and serum HBV was detected by hybridization assay and nested polymerase chain reaction.RESULTS: TTV infection was detected in 100 % of HBV-infected patients. Loss of serum TTV DNA after one year of treatment occurred in 1/16 (6 %) patients. At the end of therapy, TTV DNA was positive in 94 % of them. The decline of HBV viremia was evident at 3 months after therapy and the response rate was 31%, 44 %, 63 %, 50 % and 50 %at month 3, 6, 9, 12 and 30, respectively.CONCLUSION: TTV replication is not sensitive to lamivudine and is highly prevalent in HBV-infected patients.

Coinfection of TT virus and response to interferon therapy in patients with chronic hepatitis B or C

AIM: To investigate the serum positive percentage of TT virus (TTV) in patients with chronic hepatitis B or C and the response of the coinfected TTV to interferon (IFN) during IFN therapy for chronic hepatitis B and C. METHODS: We retrospectively studied the serum samples of 70 patients with chronic hepatitis who had received IFN-alpha therapy from January 1997 to June 2000, which included 40 cases of hepatitis B and 30 hepatitis C. All the patients had been followed up for at least 6 months after the end of IFN therapy. The serum TTV DNA was detected using the polymerase chain reaction (PCR) before and every month during the course of IFN treatment. RESULTS: TTV infection was detected in 15% (6/40) of the chronic hepatitis B group and 30% (9/30) of the chronic hepatitis C group. Loss of serum TTV DNA during IFN therapy occurred in 3 of 6 patients (50%) and 6 of 9 (67%) of hepatitis B and C groups, respectively. Seronegativity of TTV was found all during the first month of IFN therapy in the 9 patients. There was no correlation between the seroconversion of TTV and the biochemical changes of the patients. CONCLUSION: TTV is not infrequently coinfected in patients with chronic hepatitis B and C in Taiwan, and more than half of the TTV infections are IFN-sensitive. However, the loss of serum TTV DNA does not affect the clinical course of the patients with chronic hepatitis B or C.

Role of upper endoscopy in diagnosing opportunistic infections in human immunodeficiency virus-infected patients

Highly active antiretroviral therapy (HAART) has dramatically decreased opportunistic infections (OIs) in human immunodef iciency virus (HIV)-infected patients. However,gastrointestinal disease continues to account for a high proportion of presenting symptoms in these patients. Gastrointestinal symptoms in treated patients who respond to therapy are more likely to the result of drug-induced complications than OI. Endoscopic evaluation of the gastrointestinal tract remains a cornerstone of diagnosis,especially in patients with advanced immunodeficiency,who are at risk for OI. The peripheral blood CD4 lymphocyte count helps to predict the risk of an OI,with the highest risk seen in HIV-infected patients with low CD4 count (< 200 cells/mm3). This review provides an update of the role of endoscopy in diagnosing OI in the upper gastrointestinal tract in HIV-infected patients in the era of HAART.

Human Milk Oligosaccharides Enhance Innate Immunity to Respiratory Syncytial Virus and Influenza <i>in Vitro</i>

Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pathogen binding to host cell surface glycans or receptors. We investigated the effects of 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) and lacto-N-neoTetraose (LNnT) on human respiratory epithelial cell lines or peripheral blood mononuclear cells (PBMCs) following respiratory viral infectionin vitro. Expression of cytokines and viral load were monitored in infected cells. These biomarkers of innate immunity were selected since viral load and cytokine levels (IP-10, MIP-1α, IL-6, IL-8, TNF-α) have been correlated with disease severity in respiratory syncytial virus (RSV) and influenza (IAV) virus infectionin vivo. 2’FL significantly decreased RSV viral load and cytokines associated with disease severity (IL-6, IL-8, MIP-1α) and inflammation (TNF-α, MCP-1) in airway epithelial cells. LNnT and 6’SL significantly decreased IAV viral load in airway epithelial cells. 6’SL dose-dependently down-regulated IP-10 and TNF-α in RSV infected PBMCs. HMO at or below levels found in breast milk enhance innate immunity to respiratory viruses in vitro and may interact directly with cells to modulate biomarkers of innate immunity.

Innate and adaptive immune responses against picornaviruses and their counteractions: An overview

Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.

Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

Hepatitis C virus(HCV) infection is one of the mostfrequent causes of comorbidity and mortality in the human immunodeficiency virus(HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals(DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa(Peg-IFN) + ribavirin(RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCVgenotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence.

Treatment of postoperative infectious complications in patients with human immunodef iciency virus infection

BACKGROUND: Antibiotics are widely given for surgical patients to prevent infection. Because of the lack of study on the rational use of antibiotics in patients with human immunodef iciency virus(HIV)-infected during surgical procedures, we analyzed the risk factors affecting postoperative infectious complications in HIV-infected patients and explore the rational use of perioperative antibiotics.METHODS: This retrospective study consisted of 308 HIV-infected patients, 272 males and 36 females, who had undergone operation at the Shanghai Public Health Clinical Center from November 2008 to April 2012. The patients were divided into postoperative infection and non-infection groups. Their age and clinical variables were compared. The correlation between surgical incision, surgical site infection(SSI) and postoperative sepsis was analyzed. Prophylactic antibiotics were used for patients with type I and II incisions for less than 2 days. Patients with type III incisions were given antibiotics until the infection was controlled. Antiretroviral therapy(ART) was prescribed preoperatively for patients whose preoperative CD4 count was <350 cells/μL. For those patients whose preoperative CD4 count was <200 cells/μL, sulfamethoxazole and fluconazole were given preoperatively as prophylactic agents controlling Pneumocystis carinii pneumonia and fungal infection.RESULTS: A total of 196 patients developed postoperative infectious complications, and 7 patients died. Preoperative CD4 counts, ratio of CD4/CD8 cells, hemoglobin level, and postoperative CD4 counts, hemoglobin and albumin levels were risk factors of perioperative infection in HIV-infected patients. Patients with a preoperative CD4 count <200 cell/μL, anemia, a postoperative CD4 count <200 cell/μL or albumin levels <35 g/L were correlated with a higher rate of perioperative infection. There was a signif icant correlation between SSI and the type of surgical incision. The rate of SSI in patients with type I surgical incision was 2% and in those with type II surgical incision was 38%. All the patients who received type III surgical incision developed SSI, and they were more likely to develop postoperative sepsis.CONCLUSIONS: HIV-infected patients are more likely to develop postoperative infectious complications. The rational use of antibiotics in HIV-infected patients could help to reduce the rate of postoperative infectious complications in these patients.

Superior mesenteric vein thrombosis induced by influenza infection:A case report

BACKGROUND Among the various types and causes of mesenteric ischemia,superior mesenteric vein(SMV)thrombosis is a rare and ambiguous disease.If a patient presents with SMV thrombosis,past medical history should be reviewed,and the patient should be screened for underlying disease.SMV thrombosis may also occur due to systemic infection.In this report,we describe a case of SMV thrombosis complicated by influenza B infection.CASE SUMMARY A 64-year-old male visited the hospital with general weakness,muscle aches,fever,and abdominal pain.The patient underwent computed tomography(CT)and was diagnosed with SMV thrombosis.Since the patient’s muscle pain and fever could not be explained by the SMV thrombosis,the clinician performed a test for influenza,which produced a positive result for influenza B.The patient had a thrombus in the SMV only,with no invasion of the portal or splenic veins,and was clinically stable.Anticoagulation treatment was prescribed without surgery or other procedures.The follow-up CT scan showed improvement,and the patient was subsequently discharged with continued oral anticoagulant treatment.CONCLUSION This case provides evidence that influenza may be a possible risk factor for SMV thrombosis.If unexplained abdominal pain is accompanied by an influenza infection,examination of an abdominal CT scan may be necessary to screen for possible SMV thrombosis.

Integrated analysis of human influenza A(H1N1)virus infectionrelated genes to construct a suitable diagnostic model

The genome characteristics and structural functions of coding proteins correlate with the genetic diversity of the H1N1 virus,which aids in the understanding of its underlying pathogenic mechanism.In this study,analyses of the characteristic of the H1N1 virus infection-related genes,their biological functions,and infection-related reversal drugs were performed.Additionally,we used multi-dimensional bioinformatics analysis to identify the key genes and then used these to construct a diagnostic model for the H1N1 virus infection.There was a total of 169 differently expressed genes in the samples between 21 h before infection and 77 h after infection.They were used during the protein-protein interaction(PPI)analysis,and we obtained a total of 1725 interacting genes.Then,we performed a weighted gene co-expression network analysis(WGCNA)on these genes,and we identified three modules that showed significant potential for the diagnosis of the H1N1 virus infection.These modules contained 60 genes,and they were used to construct this diagnostic model,which showed an effective prediction value.Besides,these 60 genes were involved in the biological functions of this infectious virus,like the cellular response to type I interferon and in the negative regulation of the viral life cycle.However,20 genes showed an upregulated expression as the infection progressed.Other 36 upregulated genes were used to examine the relationship between genes,human influenza A virus,and infection-related reversal drugs.This study revealed numerous important reversal drug molecules on the H1N1 virus.They included rimantadine,interferons,and shikimic acid.Our study provided a novel method to analyze the characteristic of different genes and explore their corresponding biological function during the infection caused by the H1N1 virus.This diagnostic model,which comprises 60 genes,shows that a significant predictive value can be the potential biomarker for the diagnosis of the H1N1 virus infection.

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.