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Background and Objectives: The influenza A(H1N1) virus is known for large outbreaks, epidemics and pandemics worldwide owing to its genome plasticity which evolves constantly. In the year 2015 and then in 2017, India witnessed an upsurge in cases. Materials and Methods: The study was carried out in this period (2015-2017) with samples from 5 states across north India. The hemagglutinin 1 (HA1) and non-structural 1 (NS1) gene segments of the viral genome were characterised by phylogenetic analysis, selection pressure analysis, prediction of potential glycosylation sites and phylodynamic analysis of the study strains. Results: The study strains belonged to genogroup 6B. A total of 12 mutations were observed, half of which were located on the key receptor binding region of the HA1 protein. Established virulence markers D222G, S183P were observed in 2017 samples. Acquisition of an extra glycosylation site was observed in few strains from 2017 and 2016. Selection pressure analysis found the average dN/dS (v) ratio of 0.2106 and few codon sites in particular showed significant evidence of being under negative selection. Conclusion: The genogroup 6B continues to be the dominant circulating strain in Indian subcontinent region however the presence of pathogenic mutations in the 2017 strains from north India underlines the importance of continued molecular surveillance.
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INTRODUCTION: Human mastadenovirus (HAdV) types 8, 37, 64 have been considered the major contributors in Epidemic keratoconjunctivitis (EKC) epidemics, but recent surveillance data have shown the involvement of emerging recombinants, including HAdV-53, HAdV-54, and HAdV-56. In our initial work, positive samples for adenovirus revealed that our strains were closer to HAdV-54 than HAdV-8. Hence, the current study aimed to use whole genome technology to identify the HAdV strain correctly. METHODOLOGY: Oxford Nanopore technique was used, wherein a Targeted sequencing approach using long-range PCR amplification was performed. Primers were designed using HAdV-54 (AB448770.2) and HAdV-8 (AB897885.1) as reference sequences. Amplicons were sequenced on the GridION sequencer. Sequences were annotated using Gatu software, and similarities with standard reference sequence was calculated using Bioedit software. The phylogenetic tree was built after alignment in MEGA v7.0 using Neighbour joining method for each of the genes: Penton, Hexon, and Fiber. The effect of novel amino acid changes was evaluated using the PROVEAN tool. The Recombination Detection Program (RDP) package Beta 4.1 was used to identify recombinant sequences. RESULTS: Of the five samples sequenced, OL450401, OL540403, and OL540406 showed nucleotide similarity to HAdV-54 in the penton region. Additionally, OL450401 showed a statistically significant recombination event with HAdV-54 as minor and HAdV-8 as major parents. This was further supported by phylogenetic analysis as well. CONCLUSIONS: In the present study, we have found evidence of a shift from HAdV-8 towards HAdV-54, thus stressing the need for surveillance of HAdVs and to stay updated on the rise of new recombinants.
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Infecções por Adenovirus Humanos , Adenovírus Humanos , Ceratoconjuntivite , Mastadenovirus , Humanos , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/genética , Adenovírus Humanos/genética , Genoma Viral , Índia/epidemiologia , Ceratoconjuntivite/epidemiologia , Mastadenovirus/genética , Filogenia , Análise de Sequência de DNARESUMO
Respiratory samples from 139 hospitalized children were screened for the human bocavirus (HBoV) genome. Positive samples were sequenced for the partial VP1/VP2 gene followed by molecular and phylogenetic analyses. HBoV positivity was noted in 7.2% (10/139) of patients. All HBoV-positive children presented with fever, cough, and respiratory distress (90%, 9/10). Three children developed multisystemic viral illness, with one fatality. Eight children required intensive care management and five required mechanical ventilation. The nucleotide percent identity of the partial VP1/VP2 gene in the HBoV study strains ranged from 97.52% to 99.67%. Non-synonymous mutations in the VP1 protein were T591S (n = 8) and Y517S (n = 1) in the HBoV St1 strain and N475S (n = 8) and S591T (n = 2) in the HBoV St2 strain. One strain showed A556P, H556P, I561S, and M562R non-synonymous mutations. All the study strains belonged to the HBoV1 type. Seven HBoV strains belonged to the same lineage, and three belonged to another lineage. For evolutionary dynamics, GTR+I substitution model with uncorrelated relaxed lognormal clock and Bayesian Skyline tree prior showed 9.0 × 10-4 (95% highest probability density interval: 3.1 × 10-6, 2.1 × 10-3) nucleotide substitutions per site per year. Clinical suspicion and virological screening are necessary to identify HBoV infections in children.
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Bocavirus Humano , Infecções por Parvoviridae , Filogenia , Infecções Respiratórias , Centros de Atenção Terciária , Humanos , Bocavirus Humano/genética , Bocavirus Humano/classificação , Bocavirus Humano/isolamento & purificação , Infecções por Parvoviridae/virologia , Infecções por Parvoviridae/epidemiologia , Índia/epidemiologia , Feminino , Pré-Escolar , Masculino , Lactente , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Criança , Análise de Sequência de DNA , GenótipoRESUMO
In September 2022, Panchkula Civil Hospital reported an outbreak of acute febrile illness (AFI) in Pinjore, located in the Himalayan foothills, Haryana, North India. There was an upsurge of fever cases. Blood samples were taken from suspected patients (n = 58) with AFI and subjected to serology of dengue, chikungunya, Japanese encephalitis, leptospira and scrub typhus. The samples were also screened for West Nile & Zika virus RNA using real-time PCR. Viral strains were characterized by sequencing. Of the 58 cases of AFI, Dengue could be identified in 45 (77.58%) followed by JE and Chikungunya in 2 cases each (3.44%), respectively. Among Dengue positive cases, 44 had monoinfection (97.77%) and 1 patient had dengue and JE. None were positive for Zika, West Nile, Scrub typhus, and Leptospira with the testing protocol. Four patients developed dengue with warning signs, such as abdominal pain in one patient and recurrent vomiting in the remaining three. The dengue serotype could be determined in 17 samples and revealed serotype 2. Molecular evolution analysis based on the complete envelope gene revealed that all DENV-2 strains (n = 13) circulated in the outbreak area belonged to the DENV-2 cosmopoliton genotype. In the early stages of infection, relying only on clinical manifestations is ineffective, so both molecular and serological assays along with clinical diagnosis are noteworthy for determining the aetiology of AFI.
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Nucleic acid amplification tests (NAATs) have revolutionized reliable detection of dengue virus (DENV) during acute phase of infection. The study evaluated performance of CDC DENV-1-4 real-time assay, trioplex RT-PCR and heminested conventional RT-PCR assay in the diagnosis of DENV. The three NAATs were performed on 107 consecutive samples collected from patients suspected of DENV infection during acute phase of illness. Their performance was compared against composite reference standard, consisting of DENV NS1 antigen ELISA and DENV IgM ELISA. 88/107 study samples were positive by DENV ELISA, either NS1Ag (80), IgM (3) or both (5). The overall sensitivity of CDC DENV-1-4 RT-PCR assay, trioplex RT-PCR assay and conventional multiplex RT-PCR was 68.18%, 54.55% and 38.64%, respectively in diagnosing dengue during acute phase, with an area under the curve of 0.841, 0.773 and 0.693 respectively when compared against composite reference standard. The sensitivity was 82.93%, 73.17% and 51.22%, respectively within three days of illness and 60%, 42.86% and 28.57%, respectively between 4 and 5th day of illness. All the three molecular assays had 100% specificity. Maximum concordance values of 86.9% were recorded among CDC DENV-1-4 rRT-PCR assay and trioplex assay with kappa value of 0.74, suggestive of substantial agreement. CDC DENV-1-4 rRT-PCR assay can be used as a reliable and accurate test for diagnosis of DENV during acute phase of illness.
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Prior to the age of measles vaccination, infants are believed to be protected against measles by passively transferred maternal antibodies. However, the quantity and quality of such protection have not been well established in the Indian setting. We undertook this study to characterize the transfer and decline in maternal anti-measles antibodies among infants, and determine their susceptibility to measles. In this population-based, birth-cohort study, we enrolled pregnant women and their newborn infants, from a catchment area of 30 Anganwadis in Chandigarh, India. We collected maternal blood at delivery, and infant blood samples at birth, and 3, 6, and 9 months of age. Anti-measles IgG antibodies were measured using quantitative ELISA. We assessed antibody decline using log-linear models. In total, 428 mother-infant dyads were enrolled, and data from 413 dyads were analyzed. At birth, 91.5% (95% CI: 88.8, 94.2) of infants had protective antibody levels, which declined to 26.3% (95% CI: 21.0%, 31.9) at 3 months, 3.4% (95% CI: 0.9, 5.9) at 6 months, and 2.1% (95% CI: 0.1, 4.1) at 9 months. Younger mothers transferred lower levels of antibodies to their infants. We concluded that the majority of infants are susceptible to measles as early as three months of age, much earlier than their eligibility to receive measles vaccination.
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Anticorpos Antivirais , Sarampo , Recém-Nascido , Humanos , Lactente , Feminino , Gravidez , Estudos de Coortes , Estudos Prospectivos , Imunidade Materno-Adquirida , Sarampo/epidemiologia , Sarampo/prevenção & controle , Índia/epidemiologia , Vacina contra SarampoRESUMO
Epstein-Barr virus (EBV) is a nonhepatotropic virus. It causes mild self-limiting illness characterized by fever, oral ulcer, diarrhea, lymphadenopathy, and hepatosplenomegaly. Rarely it causes acute liver failure (ALF). EBV-related ALF (EBV-ALF) accounts for 0.2% of all ALF cases. The prognosis of EBV-ALF is dismal, and it can affect both immunocompromised and immunocompetent individuals. We performed a partial autopsy on a 30-year-old immunocompetent individual with infectious mononucleosis and ALF. The autopsy showed characteristic histomorphology of EBV-ALF in the form of centrizonal confluent hepatocytic necrosis, portal mixed inflammatory infiltrate, sinusoidal lymphocytosis, numerous hemophagocytic figures, and tissue Epstein-Barr encoded RNA-in situ hybridization (EBER-ISH) positivity. Extensive hemophagocytosis was noted in the liver, spleen, lymph node, and bone marrow. Other features include T-zone expansion of lymph nodes and spleen, interstitial pneumonia pattern in the lungs, and exanthematous skin changes. EBV-DNA polymerase chain reaction from the postmortem blood sample yielded 70,200 copies/µL. The index case highlights the uncommon occurrence of EBV-ALF, its histomorphological features, and its putative pathogenesis.
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Background: The phenotypical profile of cardiovascular malformations in patients with congenital rubella syndrome (CRS) is varied. We aimed to describe the profile of cardiac defects among CRS patients detected in the sentinel CRS surveillance in India during 2016-22. Methods: Sentinel sites enrolled infants with suspected CRS based on presence of cardiac defects, hearing impairment, eye signs, or maternal history of febrile rash illness. Suspected CRS cases underwent detailed systemic examination, including echocardiography and serological investigation for rubella. Cardiac defects were categorized as 'Simple' or 'Complex' as per the National Heart, Lung, and Blood Institute classification. We compared the distribution of cardiac defects among laboratory confirmed CRS cases and seronegative discarded cases. Findings: Of the 4578 suspected CRS cases enrolled by 14 sites, 558 (12.2%) were laboratory confirmed. 419 (75.1%) laboratory confirmed cases had structural heart defects (simple defects: n = 273, 65.2%, complex defects: n = 144, 34.4%), with ventricular septal defect (42.7%), atrial septal defect (39.4%), patent ductus arteriosus (36.5%), and tetralogy of Fallot as the commonest defects (4.5%). Laboratory confirmed CRS cases had higher odds of left to right shunt lesions (OR = 1.58, 95% CI: 1.15-2.17). This was mainly on account of a significant association of PDA with CRS (OR = 1.77, 95% CI: 1.42-2.21). Mortality was higher among CRS patients with complex heart defects (HR = 2.04, 95% CI: 1.26-3.30). Interpretation: Three-fourths of the laboratory confirmed CRS cases had structural heart defects. CRS patients with complex cardiac defects had higher mortality. Detecting CRS infection early and providing timely intervention for cardiovascular defects is critical for the management of CRS patients. Funding: Ministry of Health and Family Welfare, Govt of India, through Gavi, the Vaccine Alliance.
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Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.
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INTRODUCTION: Acute lower respiratory tract infections (ALRTIs) are the commonest cause of mortality in children mostly attributed to respiratory viruses. During the coronavirus disease 2019 (COVID-19) pandemic, the dynamics and transmission of infections changed worldwide due to widespread public health measures. This study aimed to understand the pattern of respiratory viruses associated with ALRTIs in children pre and during COVID-19 pandemic in India. METHODOLOGY: Respiratory samples were collected from ALRTI patients during pre-pandemic period (October 2019 to February 2020; n = 166), Delta (July 2021 to December 2021; n = 78) and Omicron wave (January 2022 to July 2022; n = 111). Samples were screened for Influenza (Inf) A pdmH1N1, InfA H3N2, InfB, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human bocavirus (hBoV), human rhinovirus (hRV), and parainfluenza virus (PIV-2 and PIV-3) by nucleic acid amplification techniques (NAATs). RESULTS: Significantly higher proportion of children with ALRTIs had virus/es isolated during pre-pandemic period than during mid-pandemic period [78.9% (131/166) vs. 52.9% (100/189); p < 0.001). RSV positivity was significantly higher (51.2%) in pre-pandemic period than 10.3% and 0.9% during the Delta and Omicron waves respectively. No significant difference in positivity rate of Inf A pdmH1N1, Inf A H3N2 and Inf B was seen. The increase in positivity of hRV (39.2% vs 42.3% vs 56.8%) and hBOV (1.2% vs 5.1% vs 9%) was documented in pre-pandemic, delta wave and omicron wave respectively. CONCLUSIONS: The COVID-19 pandemic significantly impacted the frequency and pattern of respiratory viruses among hospitalized children with ALRTIs in India.
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COVID-19 , Influenza Humana , Metapneumovirus , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Criança , Lactente , Pandemias , Vírus da Influenza A Subtipo H3N2 , COVID-19/epidemiologia , Infecções Respiratórias/epidemiologia , Vírus Sincicial Respiratório Humano/genéticaRESUMO
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections (ALRTIs). In this study, we aimed to evaluate the role of viral load, cytokines, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in determining the severity of RSV disease and identify potential biomarkers of disease severity. A total of 142 patients with RSV infection (aged between 2 months and 5 years) who presented with ALRTI between December 2013 and March 2016 were enrolled. Their nasopharyngeal aspirates were subjected to RSV viral load quantification, and local cytokine levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-17A, interferon γ (IFN-γ), and IL-10 were determined using a cytokine bead array. The levels of MMP-9 and TIMP-1 in 109 aspirates were calculated using Quantikine ELISA. These parameters were compared for different disease severity categories. A higher viral load and increased levels of TNF-α, MMP-9, and MMP-9:TIMP-1 were associated with greater severity of disease; whereas levels of IL-17A, IFN-γ, and IFN-γ:IL-10 were associated with disease resolution. When defining the transition from non-severe to severe disease, MMP-9 had a sensitivity and specificity of 89.7% and 85.4%, respectively. Moreover, MMP-9:TIMP-1 had a sensitivity and specificity of 87.2% and 76.8%, respectively. Hence, MMP-9, MMP-9:TIMP-1, TNF-α, and IL-10 could serve as potential biomarkers for disease progression in RSV-infected children.
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Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Lactente , Biomarcadores , Citocinas/análise , Interferon gama , Interleucina-10 , Interleucina-17 , Metaloproteinase 9 da Matriz , Gravidade do Paciente , Inibidor Tecidual de Metaloproteinase-1 , Fator de Necrose Tumoral alfa , Carga Viral , Pré-EscolarRESUMO
The study was planned to carry out the molecular characterization of the respiratory syncytial virus (RSV) circulating strains and to elucidate the gene expression of autophagy and mammalian target of rapamycin (mTOR) signaling pathways in children with acute lower respiratory tract infection (ALRTI). Nasopharyngeal aspirate (NPA) samples (n = 145) from children suffering from ALRTI were subjected to the detection of RSV. Of them, 31 RSV positive strains were subjected for sequencing. Semi-quantitative gene expression analysis for mTOR signaling and autophagy pathway genes was performed in respiratory tract epithelial cells using 25 RSV positive cases, and 10 age and sex matched healthy control subjects. Five representative genes were selected for each pathway and subjected to SYBR green real-time polymerase chain reaction. RSV was positive in 69 (47.6%) samples and the representative (n = 31) RSV strains belonged to RSV-A. Thirty-one strains of RSV-A on phylogenetic analysis clustered with the novel ON1 genotype having 72 bp nucleotide duplicationby targeting the ecto-domain portion of the G gene. Further, the stains belonged to lineage 1 (51.6%), followed by lineage 3 (29%) and lineage 2 (19.4%). Autophagy gene expression analysis revealed significant upregulation in NPC1 and ATG3 autophagy genes. mTOR, AKT1, and TSC1 genes of the mTOR pathway were significantly downregulated in RSV positive patients. Thus, RSV infection inducing autophagy pathway genes (NPC1 and ATG3) and suppressing mTOR signaling pathway genes (AKT1, mTOR, and TSC1) to possibly evade the host immune system through dysregulating these pathways for its way of survival within the host.
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Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Criança , Lactente , Filogenia , Vírus Sincicial Respiratório Humano/genética , Infecções por Vírus Respiratório Sincicial/genética , Genótipo , Serina-Treonina Quinases TOR/genética , Transdução de Sinais , Mucosa Respiratória , Autofagia/genéticaRESUMO
Avian influenza (AVI) is being known for its pandemic potential and devastating effects on poultry and birds. The AVI outbreaks in domesticated birds are of concern because the Low pathogenic avian influenza virus (LPAI) tends to evolve into a High pathogenic avian influenza virus (HPAI) resulting in the rapid spread and significant outbreak in poultries. The containment should be rapid and stringent precautions should be taken in handling the infected poultry cases or infected materials. In general, AVI viruses do not replicate efficiently in humans, indicating that transmitting these viruses to humans directly is a very rare preference. However, the HPAI ability to the cross-species barrier and infect humans has been known for H5N1 and H7N9. Recently, the world's first human case of transmission of the H5N8 strain from the avian species to humans has been documented. In this recent scenario, it is worth discussing the strain variations, disease severity, economic loss, and effective controlling strategies for controlling avian influenza.
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Acute encephalitis is a syndromic diagnosis. In the last two decades, a unique clinico-radiological entity, named acute encephalopathy with biphasic seizures and late restricted diffusion (AESD), has been reported in children from Asia. It is characterised by an acute febrile illness with seizures and encephalopathy, with some initial improvement followed by a second flurry of seizures and deep encephalopathy, 3-4 days later. MRI may show a pattern of 'bright tree appearance'. An aetiological agent may not always be identified but an infectious trigger is proposed. Immunomodulatory therapy has been tried with variable results. The prognosis is variable, and children are usually left with neurological sequelae including epilepsy and cognitive impairment. We describe a female infant who presented with the typical clinico-radiological syndrome of AESD and human bocavirus was identified in the stool. She received steroids and antiepileptic drugs. She has persistent cognitive impairment at follow-up but remained seizure free.
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Encefalopatias , Epilepsia , Bocavirus Humano , Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Criança , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/etiologiaRESUMO
Background and Objectives: In recent decades, the incidence of dengue has increased dramatically. In dengue-endemic countries, changes in dengue virus serotypes, genotypes, and lineages have been reported. This study was designed to detect and characterize the dengue virus isolates circulating in North India by serological and molecular techniques. Materials and Methods: This study was conducted at the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. NS1 antigen and IgM antibody against dengue were detected by ELISA methods, viral RNA was extracted and amplified by conventional PCR and one-step single-tube multiplex PCR. The purified PCR products were cycle sequenced and a database search was implemented for the confirmation of the sequence product. Phylogenetic analysis was carried out with previously reported sequences. Results: Among 1509 samples, 205 (13.6%) were found positive for IgM antibodies with the highest number (n=67) among the 21 to 30 years age group with peak positivity during post-monsoon months. Among acute samples, NS1 antigen was positive in 62.9%. Seven patients out of 13 had dengue viral RNA in PCR. It comprised six DENV-2 serotypes and one DENV-3 serotype. On phylogenetic analysis, DENV-2 strains grouped with genotype IV and DENV-3 with genotype III. Conclusion: Dengue infection was found frequently during post-monsoon season. The positivity rate of the dengue NS1 antigen test was greater than that of the antibody test. The dengue isolates were characterized as genotype IV and genotype III of DENV-2 and DENV-3 respectively.
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Viral hepatitis E is an under-estimated clinical entity with high mortality (20%-30%), especially in the third trimester of pregnancy. As complications due to hepatitis E virus (HEV) in pregnancy is much greater, it is hypothesized that HEV may cross the placenta and replicate in placental tissues even weeks after clearance from the blood, and cytokines may play a role in the immunopathogenesis of HEV in pregnancy. A total of 12 pregnant women with features of acute viral hepatitis/acute liver failure and positive for either HEV-immunoglobulin M (IgM)/HEV-RNA and 30 pregnant women negative for HEV RNA/IgM/immunoglobulin G were enrolled as study subjects and healthy controls, respectively. Following delivery, 5 ml blood was collected from the mother for HEV-RNA. Replicative RNA and viral load in placental tissue were detected through Real-Time PCR. Placental tissues from the maternal/fetal sides were stained for HEV antigen using HEV-open reading frame-2 antibody by immunohistochemistry (IHC) and for histopathological changes by haematoxylin and eosin. Plasma samples were tested for interleukin (IL)-1ß and IL-18 cytokine levels using Duo-R&D ELISA kit, whereas peripheral blood mononuclear cells were used to study the inflammasomes and IL-1ß and IL-18 cytokine genes expression.Of the 10 HEV RNA-positive sera, 9 had HEV RNA either in the maternal/fetal side of the placenta with the mean viral load of 137.4 IU/ml. Of the 10 HEV RNA-positive pregnant women, stillbirth in two and fetal and maternal death in one case was reported. IHC revealed strong brownish cytoplasmic staining (HEV antigen) in cytotrophoblasts and syncytiotrophoblast cells in positive samples. The maternal/fetal side of the infected placenta showed irregular intervillous fibrin deposition as well as tissue necrosis. The mean levels of IL-1ß and IL-18 cytokines in serum of infected subjects were significantly higher than the healthy controls (17.31 ± 4.462 vs. 8.85 ± 4.36 pg/ml; p < 0.0001*** and 2275 ± 536.9 vs. 1085 ± 531.7 pg/ml; p < 0.0001***), respectively. Detecting replicative HEV RNA and HEV antigen in placental tissues indicated the extra-hepatic replication of HEV. Furthermore, placental tissue necrosis and significant rise of cytokine levels in HEV-infected pregnant women might be contributing to the HEV pathogenesis in pregnancy.
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Vírus da Hepatite E , Hepatite E , Falência Hepática Aguda , Complicações Infecciosas na Gravidez , Citocinas , Feminino , Anticorpos Anti-Hepatite , Vírus da Hepatite E/genética , Humanos , Imunoglobulina G , Imunoglobulina M , Interleucina-18 , Leucócitos Mononucleares , Falência Hepática Aguda/complicações , Necrose , Placenta , Gravidez , Gestantes , RNA , NatimortoRESUMO
Hepatitis E contributes to 3.3 million acute hepatitis cases worldwide with 30% mortality in pregnant women. Pathogenesis of Hepatitis E is complex; thus, the present study was aimed at inflammasomes and associated cytokines in the immunopathogenesis of viral hepatitis E. PBMCs were isolated from 45 HEV IgM/HEV RNA-positive AVH/ALF and 19 healthy individuals and processed for mRNA expressions of NLRs, RLRs, and cytokines. PBMCs were cultured and stimulated with HEV-pORF-2 peptide in vitro for mRNA expression by RT-PCR and cytokines levels in serum/culture supernatant by ELISA. siRNA transfection and post-silencing effect in AVH PBMCs were also assessed by NLRP3 gene expression and IL-1ß and IL-18 levels by ELISA. The results demonstrated high viral load in ALF than AVH cases. mRNA expression of NLRP3 in AVH patients was found to be positively correlated with IL-18 (r = 0.74) and IL-1ß (r = 0.68); P < 0.0001***. Significant levels of serum IL-1ß and IL-18 cytokines were observed in AVH as compared to ALF patients. The levels of IL-1ß in the culture supernatant in mock and stimulated conditions were significantly higher in AVH than in ALF patients. Significant downregulation in NLRP3 gene expression was correlated with the reduced levels of IL-1ß and IL-18 cytokines in NLRP3-siRNA-transfected PBMCs. This study highlighted the significance of upregulated NLRP3 inflammasome leading to increased production of IL-18 and IL-1ß cytokines in sera of AVH patients. Thus, it indicated the role of Th1 response acting through the NLRP3 pathway which might have been helpful in the recovery of AVH patients. These promising results open multiple treatment avenues where specific inhibitors can be designed to modulate the progress of disease and its pathogenicity.
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Hepatite E , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Células Cultivadas , Citocinas/imunologia , Feminino , Hepatite E/imunologia , Humanos , Inflamassomos/imunologia , Gravidez , Prognóstico , Linfócitos T/imunologia , Carga ViralRESUMO
The coronavirus disease-19 has left a permanent mark on the history of the human race. Severe acute respiratory syndrome coronavirus-2 is a positive-sense single-stranded RNA virus, first reported in Wuhan, China, in December 2019 and from there took over the world. Being highly susceptible to mutations, the virus's numerous variants started to appear, and some were more lethal and infectious than the parent. The effectiveness of the vaccine is also affected severely against the new variant. In this study, the infectious mechanism of the coronavirus is explained with a focus on different variants and their respective mutations, which play a critical role in the increased transmissibility, infectivity, and immune escape of the virus. As India has already faced the second wave of the pandemic, the future outlook on the likeliness of a third wave with respect to the Indian variants such as kappa, delta, and Delta Plus is also discussed. This review article aims to reflect the catastrophe of the variants of SARS-CoV-2 and the possibility of developing even more severe variants in the near future.