ResearchPad - major-articles https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SARS-CoV-2 (COVID-19): What Do We Know About Children? A Systematic Review]]> https://www.researchpad.co/article/elastic_article_12507 Initial reports from China observed low rates of COVID-19 in children compared with adults. Emerging evidence suggests that children may be infected at the same rate as adults but are more likely to experience asymptomatic or mild disease.

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<![CDATA[Unmasking the Actual COVID-19 Case Count]]> https://www.researchpad.co/article/elastic_article_12484 This report presents a novel approach to estimate the total number of COVID-19 cases in the United States, including undocumented infections, by combining the Centers for Disease Control and Prevention’s influenza-like illness surveillance data with aggregated prescription data. We estimated that the cumulative number of COVID-19 cases in the United States by 4 April 2020 was > 2.5 million.

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<![CDATA[Increase in Methicillin-Resistant <i>Staphylococcus aureus</i> Acquisition Rate and Change in Pathogen Pattern Associated with an Outbreak of Severe Acute Respiratory Syndrome]]> https://www.researchpad.co/article/elastic_article_11684 Background. An outbreak of severe acute respiratory syndrome (SARS) occurred in our 22-bed intensive care unit (ICU; Prince of Wales Hospital, Hong Kong, HKSAR, China) from 12 March to 31 May 2003, when only patients with SARS were admitted. This period was characterized by the upgrading of infection control precautions, which included the wearing of gloves and gowns all the time, an extensive use of steroids, and a change in antibiotic prescribing practices. The pattern of endemic pathogenic organisms, the rates of acquisition of methicillin-resistant Staphylococcus aureus (MRSA), and the rates of ventilator-associated pneumonia (VAP) were compared with those of the pre-SARS and post-SARS periods.

Methods. Data on pathogenic isolates were obtained from the microbiology department (Prince of Wales Hospital). Data on MRSA acquisition and VAP rates were collected prospectively. MRSA screening was performed for all ICU patients. A case of MRSA carriage was defined as an instance in which MRSA was recovered from any site in a patient, and cases were classified as imported or ICU-acquired if the first MRSA isolate was recovered within 72 h of ICU admission or after 72 h in the ICU, respectively.

Results. During the SARS period in the ICU, there was an increase in the rate of isolation of MRSA and Stenotrophomonas and Candida species but a disappearance of Pseudomonas and Klebsiella species. The MRSA acquisition rate was also increased: it was 3.53% (3.53 cases per 100 admissions) during the pre-SARS period, 25.30% during the SARS period, and 2.21% during the post-SARS period (P < .001). The VAP rate was high, at 36.5 episodes per 1000 ventilator-days, and 47% of episodes were caused by MRSA.

Conclusions. A SARS outbreak in the ICU led to changes in the pathogen pattern and the MRSA acquisition rate. The data suggest that MRSA cross-transmission may be increased if gloves and gowns are worn all the time.

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<![CDATA[Human Bocavirus Infection in Young Children in the United States: Molecular Epidemiological Profile and Clinical Characteristics of a Newly Emerging Respiratory Virus<a href="#fn1"/>]]> https://www.researchpad.co/article/elastic_article_11679 BackgroundHuman bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as “children”) for HBoV

MethodsChildren for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1–3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004

ResultsTwenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in ⩾50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period

ConclusionsHBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children

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<![CDATA[Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis]]> https://www.researchpad.co/article/elastic_article_11676 Background. A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8d that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a.

Methods. Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a.

Results. Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis.

Conclusions. ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.

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<![CDATA[Acute Encephalopathy Associated with Influenza A Virus Infection]]> https://www.researchpad.co/article/Ne2a9367a-773a-4e79-bd3f-de3722db875d Twenty-one patients aged 4–78 years with influenza A virus–associated acute encephalopathy were studied. Influenza A virus could be detected only in a cerebrospinal fluid (CSF) specimen obtained from 1 of 18 patients, despite the use of a highly sensitive polymerase chain reaction assay. Six patients experienced influenzal encephalopathy during the course of respiratory illness. Five of these patients had hypoprothrombinemia and 4 had increased serum creatinine levels, indicating hepatic and/or renal dysfunction. Fourteen patients experienced postinfluenzal encephalopathy ⩽3 weeks after resolution of acute respiratory symptoms. In 6 patients, focal areas of high signal intensity were visible on T2-weighted magnetic resonance images of the brain. Adenovirus DNA was detected in CSF specimens obtained from 4 (36%) of 11 patients with postinfluenzal encephalopathy. Thus, influenzal encephalopathy is frequently associated with metabolic disorders, whereas postinfluenzal encephalopathy appears to have different possible etiologies.

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<![CDATA[Molecular Epidemiology of Severe Acute Respiratory Syndrome–Associated Coronavirus Infections in Taiwan<a href="#fn1"/>]]> https://www.researchpad.co/article/N8d1f2f8f-e475-40c8-9099-113397b69b45 Background In 2003, Taiwan experienced a series of outbreaks of severe acute respiratory syndrome (SARS) and 1 laboratory-contamination accident. Here we describe a new phylogenetic analytical method to study the sources and dissemination paths of SARS-associated coronavirus (SARS-CoV) infections in Taiwan

Methods A phylogenetic analytical tool for combining nucleotide sequences from 6 variable regions of a SARS-CoV genome was developed by use of 20 published SARS-CoV sequences; and this method was validated by use of 80 published SARS-CoV sequences. Subsequently, this new tool was applied to provide a better understanding of the entire complement of Taiwanese SARS-CoV isolates, including 20 previously published and 19 identified in this study. The epidemiological data were integrated with the results from the phylogenetic tree and from the nucleotide-signature pattern

Results The topologies of phylogenetic trees generated by the new and the conventional strategies were similar, with the former having better robustness than the latter, especially in comparison with the maximum-likelihood trees: the new strategy revealed that during 2003 there were 5 waves of epidemic SARS-CoV infection, which belonged to 3 phylogenetic clusters in Taiwan

Conclusions The new strategy is more efficient than its conventional counterparts. The outbreaks of SARS in Taiwan originated from multiple sources

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<![CDATA[Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children]]> https://www.researchpad.co/article/N995bb3e9-b66b-4e90-a450-bd56d19e3756 A live attenuated respiratory syncytial virus (RSV) vaccine containing a deletion of the interferon antagonist NS2 gene and mutations in the polymerase gene was well tolerated and infectious, inducing primary neutralizing antibody responses and potent memory antibody responses in RSV-seronegative children.

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<![CDATA[Neutralizing Antibodies in Patients with Severe Acute Respiratory Syndrome-Associated Coronavirus Infection]]> https://www.researchpad.co/article/N3dcab851-017a-48da-b441-5cd966e28aee Background. Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is the principal etiologic agent of SARS. We analyzed serum samples obtained from 623 patients with SARS in Beijing, to determine whether infection with SARS-CoV can elicit neutralizing antibodies (NAbs).

Methods. We developed a highly sensitive and safe neutralization assay using the SARS-CoV pseudotyped virus and used this assay to determine the titers of the NAbs in serum samples from patients with SARS.

Results. We found that 85.9% of serum samples contained NAbs against SARS-CoV and that most of the NAb activities could be attributed to immunoglobulin G. The NAbs became detectable first at 5–10 days after the onset of symptoms, and their levels peaked at 20–30 days and then were sustained for >150 days. The serum samples could neutralize the pseudotype particles bearing the spike glycoproteins from different SARS-CoV strains, suggesting that the NAbs to SARS-CoV were broadly reactive.

Conclusions. NAbs to SARS-CoV are broadly elicited in patients with SARS and, according to their kinetics, may correlate with viral load during the early stages of the disease. These results suggest that it is possible to develop effective vaccines against SARS and that NAbs provide a potential strategy for treating patients with SARS.

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<![CDATA[Association between a Novel Human Coronavirus and Kawasaki Disease]]> https://www.researchpad.co/article/Nd6a74fa8-0d4e-4bfa-95e3-759c75b05115 Kawasaki disease is a systemic vasculitis of childhood; its etiology is unknown. We identified evidence of a novel human coronavirus, designated “New Haven coronavirus” (HCoVNH), in respiratory secretions from a 6-month-old infant with classic Kawasaki disease. To further investigate the possible association between HCoV-NH infection and Kawasaki disease, we conducted a case-control study. Specimens of respiratory secretions from 8 (72.7%) of 11 children with Kawasaki disease and from 1 (4.5%) of 22 control subjects (children without Kawasaki disease matched by age and the time the specimens were obtained) tested positive for HCoVNH by reverse-transcriptase polymerase chain reaction (Mantel-Haenszel matched odds ratio, 16.0 [95% confidence interval, 3.4–74.4]; P = .0015). These data suggest that HCoV-NH infection is associated with Kawasaki disease.

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<![CDATA[Interferon-Induced Transmembrane Protein 3 Genetic Variant rs12252-C Associated With Disease Severity in Coronavirus Disease 2019]]> https://www.researchpad.co/article/Nbca07851-1b8c-4468-915b-517516aaf38c We report evidence of an age-dependent allelic association between interferon-induced transmembrane protein 3 (rs12252 allele) and severity of coronavirus disease 2019, highlighting the need for further studies and the potential for a personalized, genotype-based approach to identifying high-risk individuals.

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<![CDATA[Blinded Case‐Control Study of the Relationship between Human Coronavirus NL63 and Kawasaki Syndrome]]> https://www.researchpad.co/article/N84c0cc85-b665-4ff7-848e-7448fb421428

Abstract

We conducted a blinded, case‐control, retrospective study in pediatric patients hospitalized at The Children’s Hospital, Denver, Colorado, to determine whether human coronavirus (HCoV)–NL63 infection is associated with Kawasaki syndrome (KS). Over the course of a 7‐month period, nasopharyngeal‐wash samples from 2 (7.7%) of 26 consecutive children with KS and 4 (7.7%) of 52 matched control subjects tested positive for HCoV‐NL63 by reverse transcription–polymerase chain reaction. These data suggest that, although HCoV‐NL63 was circulating in children in our community during the time of the study, the prevalence of infection with HCoV‐NL63 was not greater in patients with KS than in control subjects.

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<![CDATA[Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody]]> https://www.researchpad.co/article/N523c03a1-e788-40fd-8304-2d7f68dca285

Abstract

We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sGHeV). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sGHeV. One of the selected antibody Fab clones, m102.4, had affinity of binding to sGHeV that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sGHeV and sGNiV. m102.4 bound a soluble form of NiV G (sGNiV) better than it bound sGHeV, and it neutralized NiV better than HeV, despite being originally selected against sGHeV. These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent

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<![CDATA[Spectrum of Viruses and Atypical Bacteria in Intercontinental Air Travelers with Symptoms of Acute Respiratory Infection]]> https://www.researchpad.co/article/N27630fbe-f31d-4772-b939-73dd4c583479

Abstract

Respiratory infections after air travel are frequent, but epidemiological data are incomplete. Using sensitive polymerase chain reactions, we studied the spectrum of atypical bacteria and respiratory viruses in travelers fulfilling the case definition of severe acute respiratory syndrome. A pathogen was identified in 67 travelers (43.2%). Influenza and parainfluenza viruses were most prevalent, at 14.2% and 15.5%, respectively. Prevalences of adenoviruses, human metapneumovirus, coronaviruses, and rhinoviruses ranged between 2.6% and 4.8%. Human bocavirus, respiratory syncytial virus, and Legionella, Mycoplasma, and Chlamydophila species were absent or appeared at frequencies of <1%. To our knowledge, these are the first specific baseline data for the mentioned agents in the context of air travel.

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<![CDATA[Epidemiological Profile and Clinical Associations of Human Bocavirus and Other Human Parvoviruses]]> https://www.researchpad.co/article/N9768861c-63c2-43ad-add6-6bd4efc9372d

Abstract

BackgroundHuman bocavirus (HBoV) and PARV4 are newly discovered human parvoviruses. HBoV, which was first detected in respiratory samples, has a potential role in the development of human respiratory disease. The present study compared the frequencies, epidemiological profiles, and clinical backgrounds of HBoV and PARV4 infections with those of other respiratory virus infections, by evaluating diagnostic samples referred to the Specialist Virology Laboratory (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom)

MethodsAnonymized samples and study subject information were obtained from the respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4, B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and parainfluenza viruses by use of nested polymerase chain reaction

ResultsHBoV infection was detected in 47 (8.2%) of 574 study subjects,&amp;ranking third in prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak incidences of HBoV were noted among infants and young children (age, 6–24 months) during the midwinter months (December and January) and were specifically associated with lower respiratory tract infections. HBoV infections were frequently accompanied by other respiratory viruses (frequency, 43%), and they were more prevalent among individuals infected with other respiratory viruses (17%), frequently adenovirus or RSV. All respiratory samples were negative for PARV4

ConclusionsIn the present study, HBoV was a frequently detected, potential respiratory pathogen, with a prevalence and an epidemiological profile comparable to those of RSV. Identification of HBoV infections may be clinically important in the future

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<![CDATA[Development and Characterization of a Severe Acute Respiratory Syndrome–Associated Coronavirus–Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice]]> https://www.researchpad.co/article/N919ec885-06d1-48fa-9071-3090ecfe19e3

Abstract

Background. Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARSCoV) could provide protection for exposed individuals.

Methods. Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection.

Results. Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed 2 antibody-binding epitopes: one MAb (201) bound within the receptor-binding domain at aa 490–510, and the other MAb (68) bound externally to the domain at aa 130–150. Mice that received 40 mg/kg of either MAb prior to challenge with SARS-CoV were completely protected from virus replication in the lungs, and doses as low as 1.6 mg/kg offered significant protection.

Conclusions. Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.

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<![CDATA[Airflow Decline after Myeloablative Allogeneic Hematopoietic Cell Transplantation: The Role of Community Respiratory Viruses]]> https://www.researchpad.co/article/N86ee7818-5074-4439-829f-f88ad5396107

Abstract

We conducted a 12-year retrospective study to determine the effects that the community respiratory-virus species and the localization of respiratory-tract virus infection have on severe airflow decline, a serious and fatal complication occurring after hematopoietic cell transplantation (HCT). Of 132 HCT recipients with respiratory-tract virus infection during the initial 100 days after HCT, 50 (38%) developed airflow decline ⩽1 year after HCT. Lower-respiratory-tract infection with parainfluenza (odds ratio [OR], 17.9 [95% confidence interval {CI}, 2.0–160]; P=.01) and respiratory syncytial virus (OR, 3.6 [95% CI, 1.0–13]; P=.05) independently increased the risk of development of airflow decline ⩽1 year after HCT. The airflow decline was immediately detectable after infection and was strongest for lower-respiratory-tract infection with parainfluenza virus; it stabilized during the months after the respiratory-tract virus infection, but, at ⩽1 year after HCT, the initial lung function was not restored. Thus, community respiratory virus–associated airflow decline seems to be specific to viral species and infection localization

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<![CDATA[Prophylaxis and Therapy for Chikungunya Virus Infection]]> https://www.researchpad.co/article/N9612edb8-faf3-4ce1-b402-259ea295ffa4

Abstract

BackgroundChikungunya virus (CHIKV) is a recently reemerged arbovirus responsible for a massive outbreak of infection in the Indian Ocean region and India that has a very significant potential to spread globally because of the worldwide distribution of its mosquito vectors. CHIKV induces a usually self-limited disease in humans that is characterized by fever, arthralgia, myalgia, and rash; however, cases of severe CHIKV infection have recently been described, particularly in adults with underlying condition and neonates born to viremic mothers

MethodsHuman polyvalent immunoglobulins were purified from plasma samples obtained from donors in the convalescent phase of CHIKV infection, and the preventive and curative effects of these immunoglobulins were investigated in 2 mouse models of CHIKV infection that we developed

ResultsCHIKV immunoglobulins contain anti-CHIKV antibodies and exhibit a high in vitro neutralizing activity and a powerful prophylactic and therapeutic efficacy against CHIKV infection in vivo, including in the neonate

ConclusionsAdministration of CHIKV immunoglobulins may constitute a safe and efficacious prevention strategy and treatment for individuals exposed to CHIKV who are at risk of severe infection, such as neonates born to viremic mothers and adults with underlying conditions. These results provide a proof-of-concept for purifying human immunoglobulins from plasma samples from patients in the convalescent phase of an emerging infectious disease for which neither prevention nor treatment is available

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<![CDATA[Mild Illness Associated with Severe Acute Respiratory Syndrome Coronavirus Infection: Lessons from a Prospective Seroepidemiologic Study of Health‐Care Workers in a Teaching Hospital in Singapore]]> https://www.researchpad.co/article/Nc681e66c-68e1-4e5d-be2a-6cbd5ce52b3a

Background. Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that has recently emerged in East Asia and North America. Although the clinical features of acute infection have been well described, mildly symptomatic or asymptomatic infections have not been well characterized.

Objective. To assess the spectrum of illness in health-care workers (HCWs).

Methods. A prospective seroepidemiologic cohort study was conducted on 372 HCWs in a large teaching hospital in Singapore who were both exposed and not exposed to patients with SARS. Participating HCWs completed a questionnaire and provided paired serum samples, which were analyzed by 2 different laboratories blinded to clinical data, by use of an enzyme-linked immunosorbent assay based on a protocol developed by the Centers for Disease Control and Prevention and a dot-blot immunoassay, with confirmation by a viral neutralization assay.

Results. A total of 21 patients with SARS were treated at our hospital. They were associated with transmission to 14 staff members, patients, and visitors in our hospital. Of the 372 HCWs participating in the present study, 8 were found to have positive antibodies to the SARS coronavirus in both samples by use of both test methods, and 6 had pneumonia and had been hospitalized for either probable or suspected SARS infection, whereas 2 had fever but did not have changes on chest radiographs. All seropositive HCWs had been exposed either directly or indirectly to patients with SARS. No asymptomatic, nonexposed staff members were found to be seropositive. There was a trend towards protection for HCWs who, while fully protected, had had contact with patients with SARS.

Conclusions. Although the majority of cases of SARS are associated with pneumonia, a small number of mildly symptomatic individuals do seroconvert. HCWs who are exposed to patients with SARS can be infected with SARS, regardless of the intensity of exposure. This has implications for surveillance and infection control planning, in the event that SARS returns next winter.

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<![CDATA[CCR5 Plays a Critical Role in the Development of Myocarditis and Host Protection in Mice Infected with Trypanosoma cruzi]]> https://www.researchpad.co/article/Nc1b0b3e3-ddf0-4000-8336-4ee67c03ff36

Abstract

The pathogenesis of myocarditis during Trypanosoma cruzi infection is poorly understood. We investigated the role played by chemokine receptor 5 (CCR5) in the influx of T cells to the cardiac tissue of T. cruzi—infected mice. mRNA and protein for the CCR5 ligands CCL3, CCL4, and CCL5 were detected in the hearts of infected mice in association with CD4+ and CD8+ T cells. There was a high level of CCR5 expression on CD8+ T cells in the hearts of infected mice. Moreover, CCR5 expression on CD8+ T cells was positively modulated by T. cruzi infection. CCR5-deficient mice infected with T. cruzi experienced a dramatically inhibited migration of T cells to the heart and were also more susceptible to infection. These results suggest that CCR5 and its ligands play a central role in the control of T cell influx in T. cruzi-infected mice. Knowledge of the mechanisms that trigger and control the migration of cells to the heart in patients with Chagas disease may help in the design of drugs that prevent myocarditis and protect against the development of severe disease.

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