Infectious diseases & immunity最新文献

{"title":"IMB-0523 Inhibits Enterovirus 71 Replication by Activating Signal Transducer and Activator of Transcription 3 Signaling to Upregulate Interferon-Stimulated Genes Expression","authors":"Hui-qiang Wang, Miao Ge, Yanping Li, Yuhuan Li, Zhuorong Li","doi":"10.1097/ID9.0000000000000072","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000072","url":null,"abstract":"Abstract Background Hand, foot, and mouth disease caused by enterovirus 71 (EV71) infection is prevalent in the Asia-Pacific region in recent years. Currently, no drug is available for the prevention and treatment of EV71 infection. IMB-0523, a N-phenylbenzamide derivative, inhibits hepatitis B virus replication by upregulating the expression of APOBEC3G. In the present study, the effect of IMB-0523 on EV71 replication and related mechanism were investigated. Methods The cytotoxicity of IMB-0523 was determined by cell counting kit. Quantitative real-time polymerase chain reaction and Western blot assay were used to detect the effect of IMB-0523 on EV71 replication and related mechanism. Cytopathic effect assay was used to investigate the effect of IMB-0523 on different EV71 strains, coxsackievirus A16, and coxsackieviruses of group B. Results The results showed that IMB-0523 could dose-dependently inhibit EV71 replication. Preliminary mechanism studies showed that IMB-0523 could activate STAT3 signaling to upregulate the expression of interferon-stimulated genes to play an antiviral role. In addition, IMB-0523 inhibited the replication of different EV71 strains, coxsackievirus A16, and coxsackieviruses of group B. Conclusions IMB-0523 inhibits EV71 replication by activating the STAT3 signaling pathway to upregulate interferon-stimulated gene expression. IMB-0523 has broad-spectrum antiviral potential and may be used as a lead compound for the development of broad spectrum antiviral drugs.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46721802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong, China","authors":"P. Guo, Y. Lan, Quanmin Li, X. Ling, Junbin Li, Xiaoping Tang, F. Hu, W. Cai, Linghua Li","doi":"10.1097/ID9.0000000000000069","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000069","url":null,"abstract":"Abstract Background With the high prevalence of pre-treatment drug resistance (PDR) and the potential impact to the virological inhibition, the detection of PDR was particularly necessary. This study aimed to determine the prevalence of PDR in Guangdong, China, and its impact on antiretroviral therapy (ART) in treatment-naive HIV patients. Methods A retrospective cohort study was conducted. A total of 1936 HIV-1–infected treatment-naive patients in the clinic of the infectious department, Guangzhou Eighth People’s Hospital, between August 2018 and December 2019 were assayed for PDR mutations before initiating ART. Patients with PDR mutations (PDR arm) were screened and compared with those without drug-resistant mutations (non-PDR arm). The rate of HIV-1 virologic failure (VF) and CD4+ T-cell counts of the 2 arms were compared at the 96th week after ART to evaluate the impact of PDR on the efficacy of ART. Results Pretreatment drug resistance was detected in 125 cases (6.46%) from the 1936 enrolled participants, most of which were resistant to non-nucleoside reverse transcriptase inhibitors (64.00%, 80/125). One hundred and eight of 125 completed the follow-up of 96 weeks (PDR arm). In this cohort, 52 patients whose ART regimen containing the resistant drug were grouped as con-PDR arm, and the remaining 56 patients whose ART regimen did not contain the resistant drug were grouped as non- con-PDR arm. A total of 125 patients without PDR were randomly selected as the control group (non-PDR arm), 112 of whom had completed the 96-week follow-up. At the 96th week after ART initiation, 7 patients (6.5%, 7/108) in the PDR arm and 1 patient (0.9%, 1/112) in the non-PDR arm developed VF, exhibiting a significant difference (χ2 = 4.901, P = 0.029). Meanwhile, 3 patients (5.8%, 3/52) in the con-PDR arm developed VF; the rate was also higher than that in the non-PDR arm, but without a significant difference (χ2 = 3.549, P = 0.095). The CD4+ T-cell count in the non-PDR arm increased more than the PDR arm (386.6 vs. 319.1 cells/μL, t = 2.448, P = 0.015) or the con-PDR arm (386.6 vs. 325.1 cells/μL, t = 1.821, P = 0.070) at 12 weeks after ART. However, no significant differences were observed in the CD4+ T-cell count from the 24th week after ART onward. Conclusions Pretreatment drug resistance was moderately prevalent in Guangdong, China, and could affect the antiretroviral efficacy during a 96-week observation period, indicating the need to closely monitor PDR before ART initiation.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48891683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric Antigen Receptor-Modified Immune Cells for Eradication of HIV Reservoirs","authors":"Guo-fen Re, Beibei Tang, Jing Kou, Chen Hong, Yi‐Qun Kuang","doi":"10.1097/ID9.0000000000000066","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000066","url":null,"abstract":"Abstract Host immune surveillance can achieve powerful clearance of infectious pathogens. Acute human immunodeficiency virus type I (HIV-1) infection can establish viral reservoirs in humans, and persistent chronic activation by the virus exhausts the immune system and ultimately causes acquired immunodeficiency syndrome. Although antiretroviral therapy (ART) can reduce the viral load and viremia in patients, latent HIV-1 reservoirs are still the biggest challenge that needs to be overcome to eradicate the virus. However, the low or absent viral antigen expression and epitope mutation caused during durable ART result in host immune escape and reservoir cell inaccessibility. In addition, durable ART accompanied by inflammation and persistent activation of immune cells, especially dysfunction and/or exhaustion of T cells. With the development of immunology, genetics, and genetic engineering technology, researchers can construct chimeric antigen receptors (CARs) to modify immune cells to enhance HIV clearance. The important research goals of creating CARs to modify natural killer (NK) and T cells are an attempt to enhance the functional effects of immune cells and restore the function of the immune system. This article reviews the latent characteristics of HIV, the development of CAR molecules, and the strategies for reprogramming T cells and NK cells with CARs, and aims to clear the HIV reservoirs and related potential problems.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61733700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Arms Race in the War Between Virus and Host: Implications for Anti-Infection Immunity.","authors":"William J Liu, Jianqing Xu","doi":"10.1097/ID9.0000000000000062","DOIUrl":"10.1097/ID9.0000000000000062","url":null,"abstract":"","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/5a/id9-2-129.PMC9295931.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Prevalent SARS-CoV-2 Antigenemia in COVID-19 Patients.","authors":"Wenyan Zhang,&nbsp;Wei Liu,&nbsp;Jiawang Lin,&nbsp;Jing Jin,&nbsp;Kefu Zhao,&nbsp;Liwei Zhu,&nbsp;Xiuzhen Wang,&nbsp;Lijie Wang,&nbsp;Renshu Tang,&nbsp;Yindi Zhu,&nbsp;Wei Zhou,&nbsp;Enqing You,&nbsp;Lei Zhang,&nbsp;Xuxiang Liu,&nbsp;Jinju Wu,&nbsp;Lili Chen,&nbsp;Wenjing Wang,&nbsp;Qiang Zhang,&nbsp;Rongbao Gao","doi":"10.1097/ID9.0000000000000057","DOIUrl":"10.1097/ID9.0000000000000057","url":null,"abstract":"<p><strong>Background: </strong>Many issues, such as severity assessment and antibody responses, remain to be answered eagerly for evaluation and understanding of COVID-19. Immune lesion is one of key pathogenesis of the disease. It would be helpful to understand the disease if an investigation on antigenemia and association was conducted in the patients with SARS-CoV-2 infection.</p><p><strong>Methods: </strong>A total of 156 patients admitted to the First People's Hospital of Hefei or Anhui Provincial Hospital on January to February 2020 were involved in this study. SARS-CoV-2 nucleocapsid (NP) antigen, specific IgM/IgG antibodies, and RNA were detected in sequential sera from three COVID-19 patients, and additional 153 COVID-19 patients by means of NP-antigen capture enzyme-linked immunosorbent assay, colloidal gold quick diagnosis, and real-time RT-PCR, respectively. The clinical types of COVID-19 patients were classified into asymptomatic, mild, moderate, severe, and critical, following on the Chinese guideline of COVID-19 diagnosis and treatment. The demographic and clinical data of patients were obtained for comparable analysis.</p><p><strong>Results: </strong>NP antigen was detected in 5 of 20 sequential sera collected from three COVID-19 patients with typically clinical symptoms, and 60.13% (92/153) expanded samples collected within 17 days after illness onset. No SARS-CoV-2 RNA segment was detected in these sera. The NP positive proportion reached a peak (84.85%, 28/33) on 6 to 8 days after illness onset. Both NP concentration and positive proportion were increased with the increase of clinical severity of COVID-19. Compared to NP negative patients, NP positive patients had older age [years, medians (interquartile ranges (IQR)), 49 (6) <i>vs.</i> 31 (11)], lower positive proportion of NP specific IgM [27.17% (25/92) <i>vs.</i> 59.02% (36/61)], and IgG [21.74% (20/92) <i>vs.</i> 59.02% (36/61)] antibodies, and longer duration [days, medians (IQR), 24 (10) <i>vs.</i> 21 (13)] from illness to recovery.</p><p><strong>Conclusions: </strong>SARS-CoV-2 NP antigenemia occurred in COVID-19, and presented highly prevalent at early stage of the disease. The antigenemia was related to clinical severity of the disease, and may be responsible for the delay of detectable SARS-Cov-2 IgM.</p>","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/5e/id9-2-193.PMC9295937.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A COVID-19 Patient Discharged According to Strict Discharge Standards: Viral Negativity in Both Nasopharynx and Feces.","authors":"Enqiang Chen,&nbsp;Lichun Wang,&nbsp;Guangming Tang,&nbsp;Menglan Wang,&nbsp;Yachao Tao,&nbsp;Ping Feng,&nbsp;Hong Tang","doi":"10.1097/ID9.0000000000000040","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000040","url":null,"abstract":"<p><p>Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) currently has spread all over the world. However, the dynamic characteristics of SARS-CoV-2 infections have not previously been described in detail. Here, we report a cured patient in West China Hospital, and describe the dynamic detection of SARS-CoV-2-RNA in different specimens and viral specific IgM and IgG antibodies in blood. The findings suggest that the fecal SARS-CoV-2-RNA negativity may be considered as a new standard for de isolation. Serum IgM and IgG antibodies detection were helpful for early diagnosis of SARS-CoV-2 infection and judgment of patients in recovery stage, respectively.</p>","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/d5/id9-2-210.PMC9295935.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC Class I Assembly Function and Intracellular Transport Routes for Hepatitis B Virus Antigen Cross-presentation by Heat Shock Protein gp96","authors":"Lijuan Qin, Yongai Liu, Yuxiu Xu, Yang Li, Jun Hu, Y. Ju, Yu Zhang, Shuo Wang, Zihai Li, Changfei Li, Xin Li, S. Meng","doi":"10.1097/ID9.0000000000000058","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000058","url":null,"abstract":"Abstract Background: During hepatitis B virus (HBV) infection, virus-infected hepatocytes directly cross-present viral antigens and regulate T cell response within the liver microenvironment. However, little is known regarding the regulatory pathways involved in viral antigen presentation in HBV-infected hepatocytes. This study investigated the underlying mechanism of antigen assembly and the HBV antigen-presenting function of major histocompatibility complex (MHC) class I molecules using heat shock protein gp96. Methods: First, western blotting, flow cytometry, co-immunoprecipitation, GST pull-down, and confocal microscopic assays were performed to determine whether endogenous gp96 affects MHC-I levels via an antigen presentation pathway. Second, the B3Z assay and an AAV/HBV-infected hepatocyte-specific gp96-deficient mouse model were used to determine whether gp96 knockout functionally impaired peptide cross-presentation and produced a weakened antiviral cytotoxic T cell (CTL) response both in vivo and in vitro. Finally, confocal microscopic analysis and the B3Z assay were employed to show that exogenous gp96-associated peptide was present in MHC-I molecules via the endoplasmic reticulum (ER)-Golgi secretory pathway. Results: Compared with the control, gp96 knockdown significantly reduced the cell surface levels of MHC-I by approximately 75% (P < 0.01). Endogenous gp96 interacts with MHC-I and is involved in antigen presentation. Moreover, a weakened antiviral CTL response (34% compared to control mice) has been observed in hepatocyte-specific gp96-deficient mice following HBV infection. gp96 directed exogenous antigen to the ER, and the exogenous gp96-chaperoned peptide was endosome- and proteasome-dependent but not transporter associated with antigen processing dependent. Conclusions: Cellular gp96 promotes the assembly and antigen presentation of MHC class I molecules. In addition, extracellular gp96 served as a natural adjuvant to induce a CTL response in a concerted and regulated manner within different cellular compartments. Our results elucidate the mechanism of assembly of MHC class I molecules by gp96, which may be beneficial for the design of immunotherapy and vaccines.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41588115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Acute Hepatitis of Unknown Etiology in Children: Is It Caused by Pathogens or Non-infectious Factors?","authors":"Wei Hu,&nbsp;Min Zhang,&nbsp;Zhe Xu,&nbsp;Jing Li,&nbsp;Fu-Sheng Wang,&nbsp;Tong Li","doi":"10.1097/ID9.0000000000000060","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000060","url":null,"abstract":"<p><p>Recently, an outbreak of severe acute hepatitis of unknown etiology in children has been reported in more than 27 countries worldwide. However, information on its prevalence in different countries and regions is still lacking. The evidence is suggestive of a potential viral infection, but this has not been fully confirmed. Cases of this disease have been reported in children, mainly in those younger than 5 years old. The reason for the age range of the disease requires further investigation.</p>","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/e0/id9-2-200.PMC9295934.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate Immune Response in Respiratory System: A Double-edged Sword Against Virus Infection.","authors":"Ang Li,&nbsp;Jianqing Xu","doi":"10.1097/ID9.0000000000000031","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000031","url":null,"abstract":"Respiratory virus infection, as a leading cause of newly emerging or re-emerging infectious diseases, is undoubtedly a primary threat for global public health. Nevertheless, among various respiratory viruses, namely adenovirus, influenza virus, rhinovirus, respiratory syncytial virus as well as coronavirus, most of them cause self-limited diseases with mild symptoms. However, a fewmay progress into severe morbidity and evenmortality. For example, a-coronavirus HCoV-229E, HCoV-NL63 and ßcoronavirus HCoV-OC43, HCoV-HKU1 only cause mild common cold, whereas the b-coronavirus SARS-CoV, MERSCoV, and SARS-CoV-2 could result in fatal infection and pose great threat to human public health with global pandemics. Similar observations exist for influenza viruses, as low pathogenic seasonal influenza (H3N2) versus high pathogenic avian influenza (H5N1 and H7N9) and 1918 pandemic influenza (H1N1). The mechanisms underlying the nature of different respiratory viral infections should be urgently explored to develop effective intervention approaches.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/7a/id9-2-132.PMC9295932.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and Clinical Management of Acute Severe Hepatitis of Unknown Origin: Operational Recommendation of Peking Union Medical College Hospital.","authors":"Wei Cao,&nbsp;Zhenghong Li,&nbsp;Huadong Zhu,&nbsp;Xiang Zhou,&nbsp;Qiwen Yang,&nbsp;Yang Han,&nbsp;Jihai Liu,&nbsp;Qing Chang,&nbsp;Taisheng Li","doi":"10.1097/ID9.0000000000000061","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000061","url":null,"abstract":"<p><p>Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022, which has exceeded the past annual incidences of related regions, and has aroused wide concern. Affected patients were predominantly children under 16 years of age, presented with symptoms of acute hepatitis with markedly elevated liver enzymes, and had been ruled out of common viral infections such as hepatitis A, B, C, D, and E. Similar cases have not been reported in China yet. However, considering that the severe acute hepatitis has involved worldwide areas, still with unknown origin, and incidences of severity is relatively high, we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital, to get fully prepared to the possible public health events.</p>","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/ed/id9-2-179.PMC9295933.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}