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1.
Med Sci Monit ; 29: e939580, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722047

RESUMO

In November 2021, the World Health Organization (WHO) first identified the Omicron variant of SARS-CoV-2, B.1.1.529, as a variant of concern (VOC). By early 2022, the Omicron variant and its five lineages, BA.1, BA.2, BA.3, BA.4. and BA.5, had become the predominant cause of COVID-19 in most countries. The Omicron XBB.1.5 subvariant is a sublineage of the XBB variant, a recombinant of two BA.2 sublineages, with the F486P mutation in the spike protein that increases infectivity due to increased binding affinity to the angiotensin-converting enzyme 2 (ACE2) receptor. On the week ending 21 January 2023, the XBB.1.5 subvariant caused 49.1% of cases of COVID-19 in the US. The rapid rise in the prevalence of this subvariant may be explained by immune escape to previous infection or vaccines, spike mutations in F486P, and increased affinity for the ACE2 receptor. Also, current booster vaccines may not provide adequate protection from infection from this subvariant, which has been named by the media as the 'Kraken' subvariant. This Editorial aims to present the current status of the XBB.1.5 subvariant of Omicron SARS-CoV-2 and the reasons for, and implications of, its rapid global spread.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2/genética , COVID-19/epidemiologia , COVID-19/virologia , Mutação , SARS-CoV-2/genética
2.
Cancer Discov ; 13(1): 17-18, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36620882

RESUMO

SUMMARY: Chronic infection by several "high-risk" human papillomavirus (HPV) types has been causally implicated in several forms of anogenital and oropharyngeal cancers. Now, HPV42, which is usually classified as a "low-risk" type, can be listed as the main cause of digital papillary adenocarcinoma, an uncommon malignant tumor of the fingers and toes. See related article by Leiendecker et al., p. 70 (3).


Assuntos
Adenocarcinoma Papilar , Neoplasias Ósseas , Neoplasias da Mama , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Feminino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias Orofaríngeas/virologia , Células Germinativas/patologia
4.
PLoS One ; 18(1): e0278675, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649247

RESUMO

BACKGROUND: HIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya. METHODS: We conducted a nested study of 62 HIV-uninfected and 64 healthy women living with HIV, as well as their HIV-exposed uninfected (N = 61) and HIV-unexposed (N = 64) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between May 1, 2020-February 1, 2022 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on available stool samples from seropositive participants. RESULTS: SARS-CoV-2 seropositivity was found in 66% of the 126 mothers and in 44% of the 125 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR] = 0.810, 95% CI: 0.517-1.27) or infant HIV exposure (HR = 1.47, 95% CI: 0.859-2.53). Maternal SARS-CoV-2 was associated with a two-fold increased risk of infant infection (HR = 2.31, 95% CI: 1.08-4.94). Few participants (13% mothers, 33% infants) had symptoms; no participant experienced severe COVID-19 or death. Seroreversion occurred in about half of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants. CONCLUSIONS: These data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection and that antibody responses waned over an average of 8-10 months. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.


Assuntos
COVID-19 , Infecções por HIV , Feminino , Humanos , Lactente , COVID-19/epidemiologia , COVID-19/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Quênia/epidemiologia , Período Pós-Parto , Estudos Prospectivos , RNA Viral/análise , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Estudos de Casos e Controles , Fezes/virologia , Reação em Cadeia da Polimerase
5.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649525

RESUMO

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is closely related to the diagnostic stage. Due to the difficulty diagnosing early-stage HCC, most patients with HCC are diagnosed at the advanced stage. In this study, we used protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T-Bil) to establish a novel diagnostic model for early-stage hepatitis B virus (HBV)-related HCC. METHODS: The serum levels of PIVKA-II, AFP, AST, ALT, and T-Bil were measured in 148 patients with early-stage HBV-related HCC and 940 patients with chronic hepatitis B. The receiver operating characteristic (ROC) curves were used to verify the diagnostic efficacy of the novel diagnostic model for early-stage HBV-related HCC. RESULTS: The mathematical model of [1.5 x PIVKA-II/(AST x T-Bil) + AFP/(ALT x T-Bil)] was selected as the novel diagnostic model. The areas under ROC curves (AUROCs) of the novel diagnostic model for detecting early-stage HBV-related HCC were significantly higher than those of PIVKA-II, AFP, and PIVKA-II combined with AFP (HCC ≤ 5 cm: 0.925 vs. 0.826, 0.666, and 0.821; HCC < 3 cm: 0.896 vs. 0.741, 0.651, and 0.765, respectively) (all p < 0.001). Using serum levels of AFP ≥ 20 ng/mL, the diagnostic model had the highest AUROC values of 0.960 and 0.933 for HCC ≤ 5 cm (89 cases) and HCC < 3 cm (40 cases), respectively, with a sensitivity of 83.15%, and 77.50% and specificity of 95.34% and 90.69%, respectively. CONCLUSIONS: The novel diagnostic model is superior to PIVKA-II and AFP for diagnosing early-stage HBV-related HCC, especially in patients with abnormal serum AFP levels.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas/metabolismo , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Protrombina , Curva ROC , Hepatite B/complicações
6.
J Obstet Gynaecol ; 43(1): 2162867, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36651606

RESUMO

Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that reported adverse pregnancy outcomes in pregnant women with COVID-19 infection. A literature search was performed in PubMed and Scopus up to 1 September 2022, for retrieving original articles published in the English language assessing the association between COVID-19 infection and adverse pregnancy outcomes. Finally, in this review study, of 1790 articles obtained in the initial search, 141 eligible studies including 1,843,278 pregnant women were reviewed. We also performed a meta-analysis of a total of 74 cohort and case-control studies. In this meta-analysis, both fixed and random effect models were used. Publication bias was also assessed by Egger's test and the trim and fill method was conducted in case of a significant result, to adjust the bias. The result of the meta-analysis showed that the pooled prevalence of preterm delivery, maternal mortality, NICU admission and neonatal death in the group with COVID-19 infection was significantly more than those without COVID-19 infection (p<.01). A meta-regression was conducted using the income level of countries. COVID-19 infection during pregnancy may cause adverse pregnancy outcomes including of preterm delivery, maternal mortality, NICU admission and neonatal death. Pregnancy loss and SARS-CoV2 positive neonates in Lower middle income are higher than in High income. Vertical transmission from mother to foetus may occur, but its immediate and long-term effects on the newborn are unclear.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez , COVID-19/complicações , COVID-19/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Morte Perinatal/etiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/virologia , SARS-CoV-2/isolamento & purificação , Mortalidade Materna , Unidades de Terapia Intensiva Neonatal , Admissão do Paciente/estatística & dados numéricos
7.
Science ; 379(6627): 11-12, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36603077
8.
Antiviral Res ; 210: 105515, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603773

RESUMO

PREAMBULAR NOTA BENE: As a tribute to Dr Mike Bray, the following review of literature willbe mainly based on published data andconcepts, but will also contain my personal views, and in this respect could be more considered as a bioassay. Even though a cost-effective and excellent prophylactic vaccine exists since many years to protect against hepatitis B virus (HBV) infection, academic-researcher/drug-developers/stakeholders are still busy with the R&D of novel therapies that could eventually have an impact on its worldwide incidence. The Taiwanese experience have univocally demonstrated the effectiveness of constrained national HBV prophylactic vaccination programs to prevent the most dramatic HBV-induced end-stage liver disease, which is hepatocellular carcinoma; but yet the number of individuals chronically infected with the virus, for whom the existing prophylactic vaccine is no longer useful, remains high, with around 300 million individuals around the globe. In this review/bioassay, recent findings and novel concepts on prospective therapies against HBV infections will be discussed; yet it does not have the pretention to be exhaustive, as "pure immunotherapeutic concepts" will be mainly let aside (or referred to other reviews) due to a lack of expertise of this writer, but also due to the lack of, or incremental, positive results in clinical trials as-off today with these approaches.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/virologia , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia
9.
Cochrane Database Syst Rev ; 1: CD015167, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700518

RESUMO

BACKGROUND: Hyperimmune immunoglobulin (hIVIG) contains polyclonal antibodies, which can be prepared from large amounts of pooled convalescent plasma or prepared from animal sources through immunisation. They are being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). This review was previously part of a parent review addressing convalescent plasma and hIVIG for people with COVID-19 and was split to address hIVIG and convalescent plasma separately. OBJECTIVES: To assess the benefits and harms of hIVIG therapy for the treatment of people with COVID-19, and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Research Database, the Cochrane COVID-19 Study Register, the Epistemonikos COVID-19 L*OVE Platform and Medline and Embase from 1 January 2019 onwards. We carried out searches on 31 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated hIVIG for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies that evaluated standard immunoglobulin. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used RoB 2. We rated the certainty of evidence, using the GRADE approach, for the following outcomes: all-cause mortality, improvement and worsening of clinical status (for individuals with moderate to severe disease), quality of life, adverse events, and serious adverse events. MAIN RESULTS: We included five RCTs with 947 participants, of whom 688 received hIVIG prepared from humans, 18 received heterologous swine glyco-humanised polyclonal antibody, and 241 received equine-derived processed and purified F(ab')2 fragments. All participants were hospitalised with moderate-to-severe disease, most participants were not vaccinated (only 12 participants were vaccinated). The studies were conducted before or during the emergence of several SARS-CoV-2 variants of concern. There are no data for people with COVID-19 with no symptoms (asymptomatic) or people with mild COVID-19. We identified a further 10 ongoing studies evaluating hIVIG. Benefits of hIVIG prepared from humans We included data on one RCT (579 participants) that assessed the benefits and harms of hIVIG 0.4 g/kg compared to saline placebo. hIVIG may have little to no impact on all-cause mortality at 28 days (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.43 to 1.44; absolute effect 77 per 1000 with placebo versus 61 per 1000 (33 to 111) with hIVIG; low-certainty evidence). The evidence is very uncertain about the effect on worsening of clinical status at day 7 (RR 0.85, 95% CI 0.58 to 1.23; very low-certainty evidence). It probably has little to no impact on improvement of clinical status on day 28 (RR 1.02, 95% CI 0.97 to 1.08; moderate-certainty evidence). We did not identify any studies that reported quality-of-life outcomes, so we do not know if hIVIG has any impact on quality of life. Harms of hIVIG prepared from humans hIVIG may have little to no impact on adverse events at any grade on day 1 (RR 0.98, 95% CI 0.81 to 1.18; 431 per 1000; 1 study 579 participants; low-certainty evidence). Patients receiving hIVIG probably experience more adverse events at grade 3-4 severity than patients who receive placebo (RR 4.09, 95% CI 1.39 to 12.01; moderate-certainty evidence). hIVIG may have little to no impact on the composite outcome of serious adverse events or death up to day 28 (RR 0.72, 95% CI 0.45 to 1.14; moderate-certainty evidence). We also identified additional results on the benefits and harms of other dose ranges of hIVIG, not included in the summary of findings table, but summarised in additional tables. Benefits of animal-derived polyclonal antibodies We included data on one RCT (241 participants) to assess the benefits and harms of receptor-binding domain-specific polyclonal F(ab´)2 fragments of equine antibodies (EpAbs) compared to saline placebo. EpAbs may reduce all-cause mortality at 28 days (RR 0.60, 95% CI 0.26 to 1.37; absolute effect 114 per 1000 with placebo versus 68 per 1000 (30 to 156) ; low-certainty evidence). EpAbs may reduce worsening of clinical status up to day 28 (RR 0.67, 95% CI 0.38 to 1.18; absolute effect 203 per 1000 with placebo versus 136 per 1000 (77 to 240); low-certainty evidence). It may have some effect on improvement of clinical status on day 28 (RR 1.06, 95% CI 0.96 to 1.17; low-certainty evidence). We did not identify any studies that reported quality-of-life outcomes, so we do not know if EpAbs have any impact on quality of life. Harms of animal-derived polyclonal antibodies EpAbs may have little to no impact on the number of adverse events at any grade up to 28 days (RR 0.99, 95% CI 0.74 to 1.31; low-certainty evidence). Adverse events at grade 3-4 severity were not reported. Individuals receiving EpAbs may experience fewer serious adverse events than patients receiving placebo (RR 0.67, 95% CI 0.38 to 1.19; low-certainty evidence). We also identified additional results on the benefits and harms of other animal-derived polyclonal antibody doses, not included in the summary of findings table, but summarised in additional tables. AUTHORS' CONCLUSIONS: We included data from five RCTs that evaluated hIVIG compared to standard therapy, with participants with moderate-to-severe disease. As the studies evaluated different preparations (from humans or from various animals) and doses, we could not pool them. hIVIG prepared from humans may have little to no impact on mortality, and clinical improvement and worsening. hIVIG may increase grade 3-4 adverse events. Studies did not evaluate quality of life. RBD-specific polyclonal F(ab´)2 fragments of equine antibodies may reduce mortality and serious adverse events, and may reduce clinical worsening. However, the studies were conducted before or during the emergence of several SARS-CoV-2 variants of concern and prior to widespread vaccine rollout. As no studies evaluated hIVIG for participants with asymptomatic infection or mild disease, benefits for these individuals remains uncertain. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence.


Assuntos
COVID-19 , Imunoglobulinas , Humanos , COVID-19/terapia , COVID-19/virologia , Imunoglobulinas/uso terapêutico , SARS-CoV-2/genética , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Phytomedicine ; 109: 154549, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610129

RESUMO

BACKGROUND: Acute lung injury (ALI) is a common complication of sepsis with poor effective interventions. Huashibaidu formula (HSBD) showed good therapeutic effects in treating coronavirus disease 2019 (COVID-19) patients. PURPOSE: This study was designed to investigate the therapeutic potential and precise mechanism of HSBD against sepsis-induced ALI based on network pharmacology and animal experiments. MATERIALS AND METHODS: Network pharmacology was used to predict the possible mechanism of HSBD against sepsis. Next, a sepsis-induced ALI rat model via intraperitoneal lipopolysaccharide (LPS) was constructed to evaluate the level of inflammatory cytokines and the degree of lung injury. The expression of inflammation-related signaling pathways, including TLR4/NF-κB and PI3K/Akt was determined by western blot. RESULTS: Network pharmacology analysis indicated that HSBD might have a therapeutic effect on sepsis mainly by affecting inflammatory and immune responses. Animal experiments demonstrated that HSBD protected the lung tissue from LPS-induced injury, and inhibited the levels of inflammatory cytokines such as interleukin (IL)-1ß, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the serum and IL-1ß, IL-5, IL-6, IL-18, GM-CSF, IFN-γ and TNF-α in the lung tissue. Western blot results revealed that HSBD downregulated the expression of TLR4/NF-κB and upregulated the expression of PI3K/Akt. CONCLUSION: The therapeutic mechanism of HSBD against sepsis-induced ALI mainly involved suppressing cytokine storms and relieving inflammatory symptoms by regulating the expression of TLR4/NF-κB and PI3K/Akt. Our study provides a scientific basis for the mechanistic investigation and clinical application of HSBD in the treatment of sepsis and COVID-19.


Assuntos
Lesão Pulmonar Aguda , Síndrome da Liberação de Citocina , Sepse , Animais , Ratos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , COVID-19 , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Citocinas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Med Oncol ; 40(2): 78, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635412

RESUMO

Cervical cancer is a heterogeneous malignancy mainly caused by human papillomavirus (HPV). While a few studies have revealed heterogeneity of cervical cancer in chromosome levels, the correlation between genetic heterogeneity and HPV integration in cervical cancer remains unknown. Here, we applied multi-region whole-exome sequencing and HPV integration analysis to explore intratumor heterogeneity in cervical cancer. We sequenced 20 tumor regions and 5 adjacent normal tissues from 5 cervical cancer patients, analysis based on somatic mutations and somatic copy number alterations (SCNAs) levels were performed. Variable heterogeneity was observed between the five patients with different tumor stages and HPV infection statuses. We found HPV integration has a positive effect on somatic mutation burden, but the relation to SCNAs remains unclear. Frequently mutated genes in cervical cancer were identified as trunk events, such as FBXW7, PIK3CA, FAT1 in somatic mutations and TP63, MECOM, PIK3CA, TBL1XR1 in SCNAs. New potential driver genes in cervical cancer were summarized including POU2F2, TCF7 and UBE2A. The SCNAs level has potential relation with tumor stage, and Signature 3 related to homologous recombination deficiency may be the appropriate biomarker in advanced cervical cancer. Mutation signature analysis also revealed a potential pattern that APOBEC-associated signature occurs in early stage and signatures associated with DNA damage repair arise at the later stage of cervical cancer evolution. In a conclusion, our study provides insights into the potential relationship between HPV infection and tumor heterogeneity. Those results enhanced our understanding of tumorigenesis and progression in cervical cancer.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Evolução Clonal/genética , Variações do Número de Cópias de DNA , Mutação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
18.
Viruses ; 15(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36680207

RESUMO

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all the previously emerged variants. The numerous mutations in Omicron's viral genome and its sub-lineages attribute it a larger amount of viral fitness, owing to the alteration of the transmission and pathophysiology of the virus. With a rapid change to the viral structure, Omicron and its sub-variants, namely BA.1, BA.2, BA.3, BA.4, and BA.5, dominate the community with an ability to escape the neutralization efficiency induced by prior vaccination or infections. Similarly, several recombinant sub-variants of Omicron, namely XBB, XBD, and XBF, etc., have emerged, which a better understanding. This review mainly entails the changes to Omicron and its sub-lineages due to it having a higher number of mutations. The binding affinity, cellular entry, disease severity, infection rates, and most importantly, the immune evading potential of them are discussed in this review. A comparative analysis of the Delta variant and the other dominating variants that evolved before Omicron gives the readers an in-depth understanding of the landscape of Omicron's transmission and infection. Furthermore, this review discusses the range of neutralization abilities possessed by several approved antiviral therapeutic molecules and neutralizing antibodies which are functional against Omicron and its sub-variants. The rapid evolution of the sub-variants is causing infections, but the broader aspect of their transmission and neutralization has not been explored. Thus, the scientific community should adopt an elucidative approach to obtain a clear idea about the recently emerged sub-variants, including the recombinant variants, so that effective neutralization with vaccines and drugs can be achieved. This, in turn, will lead to a drop in the number of cases and, finally, an end to the pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/terapia , COVID-19/virologia , Mutação , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus , Evasão da Resposta Imune
19.
Viruses ; 15(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36680201

RESUMO

Human adenovirus (HAdV) is extremely common and can rapidly spread in confined populations such as daycare centers, hospitals, and retirement homes. Although HAdV usually causes only minor illness in otherwise healthy patients, HAdV can cause significant morbidity and mortality in certain populations, such as the very young, very old, or immunocompromised individuals. During infection, the viral DNA undergoes dramatic changes in nucleoprotein structure that promote the rapid expression of viral genes, replication of the DNA, and generation of thousands of new infectious virions-each process requiring a distinct complement of virus and host-encoded proteins. In this review, we summarize our current understanding of the nucleoprotein structure of HAdV DNA during the various phases of infection, the cellular proteins implicated in mediating these changes, and the role of epigenetics in HAdV gene expression and replication.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Nucleoproteínas , Humanos , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/genética , Expressão Gênica , Nucleoproteínas/genética , Replicação Viral
20.
Viruses ; 15(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680268

RESUMO

The cessation of measles virus (MeV) vaccination in more than 40 countries as a consequence of the COVID-19 pandemic is expected to significantly increase deaths due to measles. MeV can infect the central nervous system (CNS) and lead to lethal encephalitis. Substantial part of virus sequences recovered from patients' brain were mutated in the matrix and/or the fusion protein (F). Mutations of the heptad repeat domain located in the C terminal (HRC) part of the F protein were often observed and were associated to hyperfusogenicity. These mutations promote brain invasion as a hallmark of neuroadaptation. Wild-type F allows entry into the brain, followed by limited spreading compared with the massive invasion observed for hyperfusogenic MeV. Taking advantage of our ex vivo models of hamster organotypic brain cultures, we investigated how the hyperfusogenic mutations in the F HRC domain modulate virus distribution in CNS cells. In this study, we also identified the dependence of neural cells susceptibility on both their activation state and destabilization of the virus F protein. Type I interferon (IFN-I) impaired mainly astrocytes and microglial cells permissiveness contrarily to neurons, opening a new way of consideration on the development of treatments against viral encephalitis.


Assuntos
Sistema Nervoso Central , Vírus do Sarampo , Sarampo , Animais , Cricetinae , Humanos , Encéfalo , Sistema Nervoso Central/virologia , Interferons/metabolismo , Vírus do Sarampo/fisiologia , Proteínas Virais de Fusão/genética
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