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1.
PLoS Biol ; 19(11): e3001423, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34735435

RESUMO

Herpesviruses cause severe diseases particularly in immunocompromised patients. Both genome packaging and release from the capsid require a unique portal channel occupying one of the 12 capsid vertices. Here, we report the 2.6 Å crystal structure of the pentameric pORF19 of the γ-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) resembling the portal cap that seals this portal channel. We also present the structure of its ß-herpesviral ortholog, revealing a striking structural similarity to its α- and γ-herpesviral counterparts despite apparent differences in capsid association. We demonstrate pORF19 pentamer formation in solution and provide insights into how pentamerization is triggered in infected cells. Mutagenesis in its lateral interfaces blocked pORF19 pentamerization and severely affected KSHV capsid assembly and production of infectious progeny. Our results pave the way to better understand the role of pORF19 in capsid assembly and identify a potential novel drug target for the treatment of herpesvirus-induced diseases.


Assuntos
Herpesvirus Humano 8/fisiologia , Fases de Leitura Aberta/genética , Multimerização Proteica , Proteínas Virais/metabolismo , Montagem de Vírus/fisiologia , Animais , Capsídeo/química , Sequência Conservada , Cristalografia por Raios X , Empacotamento do DNA , DNA Viral/genética , Drosophila , Células HEK293 , Herpesvirus Humano 8/ultraestrutura , Humanos , Modelos Moleculares , Mutagênese/genética , Proteínas Mutantes/metabolismo , Proteínas Virais/química
2.
BMC Microbiol ; 22(1): 301, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36510121

RESUMO

BACKGROUND: Large-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as type 2 diabetes (T2D). To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where T2D prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 T2D and 119 non-T2D participants from the Eastern Province of Saudi Arabia. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples based on diabetes status and glucose level. RESULTS: In this study we performed the largest microbiome study ever conducted in Saudi Arabia, as well as the first-ever characterization of gut microbiota T2D versus non-T2D in this population. We observed overall positive enrichment within diabetics compared to healthy individuals and amongst diabetic participants; those with high glucose levels exhibited slightly more positive enrichment compared to those at lower risk of fasting hyperglycemia. In particular, the genus Firmicutes was upregulated in diabetic individuals compared to non-diabetic individuals, and T2D was associated with an elevated Firmicutes/Bacteroidetes ratio, consistent with previous findings. CONCLUSION: Based on diabetes status and glucose levels of Saudi participants, relatively stable differences in stool composition were perceived by differential abundance and alpha diversity measures. However, community level differences are evident in the Saudi population between T2D and non-T2D individuals, and diversity patterns appear to vary from well-characterized microbiota from Western cohorts. Comparing overlapping and varying patterns in gut microbiota with other studies is critical to assessing novel treatment options in light of a rapidly growing T2D health epidemic in the region. As a rapidly emerging chronic condition in Saudi Arabia and the Middle East, T2D burdens have grown more quickly and affect larger proportions of the population than any other global region, making a regional reference T2D-microbiome dataset critical to understanding the nuances of disease development on a global scale.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Microbiota , Humanos , RNA Ribossômico 16S/genética , Microbioma Gastrointestinal/genética , Glucose
3.
Medicina (Kaunas) ; 58(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36363580

RESUMO

Background and Objectives: Respiratory syncytial virus (RSV) is a major cause of morbidity and hospital admission due to respiratory tract infection among infants and young children. The current study aims to describe the prevalence and the seasonal pattern of RSV during the previous seven years. Materials and Methods: Clinical data and RSV antigen and PCR test results were collected from patients' medical records at King Fahd Hospital of the University in the Eastern Province of Saudi Arabia between January 2015 and February 2022. Results: The overall percentage of RSV detection was 26.3% (336/1279) among the tested individuals. RSV infection was more common among children below five years and elderly above 60 years of age. Two-thirds of the cases required hospitalization. The average hospital stay due to RSV infection was 6.5 days (range 0−56 days). The rate of hospitalization was higher among infants and younger children and decreased with age (p-value < 0.001). RSV infection was more prevalent between August and February and decreased appreciably between March and July. The peak level of infection was during December and January. No RSV infections were reported during the COVID-19 pandemic and the following winter. The cases increased again in August 2021, with an unusual out-of-season peak. Conclusions: RSV infection is one of the important causes of morbidity and hospitalization among infants and young children in Saudi Arabia. The seasonal pattern of infection has changed after the COVID-19 pandemic, and the physicians should be aware that infection may happen currently at different times throughout the year.


Assuntos
COVID-19 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Criança , Humanos , Pré-Escolar , Idoso , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estações do Ano , COVID-19/epidemiologia , Centros de Atenção Terciária , Arábia Saudita/epidemiologia , Pandemias , Hospitalização
4.
Malays J Med Sci ; 28(6): 100-107, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35002494

RESUMO

BACKGROUND: Pooled specimen screening for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can improve laboratory testing capacity. This study assessed the impact of pooling and retesting individual swabs on the overall detection rate and reduction in the frequency of retesting. METHODS: One hundred respiratory swabs specimens were tested individually and in pools of three or five samples using the Cepheid's Xpert® Xpress SARS-CoV-2 test kit. The optimum number of samples per pool was calculated using the application 'A Shiny App for Pooled Testing'. RESULTS: Twenty-five pools were generated from 101 samples. Out of 13 pools that contained five samples each, three pools gave true positive results. While out of the 12 pools that contained three samples each, five pools gave true positive results. Four samples gave a false negative pool result. The overall sensitivity and specificity of the assay in the pools were 66.6% and 100%, respectively. The cycle threshold was reduced in most of the pools compared to individual sample tests. CONCLUSION: The overall pooled test had a remarkable impact on laboratory resources. Yet, caution is warranted when selecting the cases for pooled testing, since the reduction in sensitivity can significantly impact and increase the risk of exposure to infection.

5.
Breast Cancer Res Treat ; 173(1): 87-91, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30306427

RESUMO

PURPOSE: KAI1 (also called CD82) is a metastasis suppressor gene known to be downregulated in breast cancer and other solid tumors. The downregulation of KAI1 or loss of its function is usually associated with bad prognosis. The mechanism behind KAI1 loss of function is complex. In this study, we investigated "alternative splicing" as a possible mechanism that underlies KAI1 loss of function in breast cancer patients from a tertiary hospital in Saudi Arabia. METHODS: Expression of KAI1 was studied in FFPE breast cancer and control tissue sections by IHC using two different antibodies targeting different domains of the protein. The TS82B antibody targets the extracellular loop, which constitutes most of the protein, while the second EPR4112 antibody targets the C-terminal intracellular domain of the protein. RESULTS: Out of 90 breast cancer samples, 67% showed loss of KAI1 expression. The remaining 33% showed KAI1 expression with (TS82B) antibody; however, the protein was detected in only 11% of cancers when using the antibody (EPR4112) indicating a truncation of the protein at the C-terminus (truncated-KAI1) in 22% of the studied cancer samples. A significant correlation was found between truncated-KAI1 expression and advanced cancer stage (association with lymph node metastasis, P value 0.008). CONCLUSION: Alternative splicing is an important mechanism underlying KAI1 loss of function in breast cancer, and it is associated with bad prognosis (advanced cancer stage).


Assuntos
Processamento Alternativo , Neoplasias da Mama/genética , Proteína Kangai-1/genética , Proteína Kangai-1/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Mutação com Perda de Função , Pessoa de Meia-Idade , Arábia Saudita
6.
J Water Health ; 17(1): 72-83, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30758305

RESUMO

Bacterial community diversity of bulk water and corresponding biofilms of four intensive care units' (ICUs) drinking water systems were studied and compared using 16S rRNA gene amplicons and next generation sequencing. Proteobacteria, mainly Alphaproteobacteria and Betaproteobacteria were dominant in the bulk water and biofilms. Principal component analysis showed different bacterial communities characterizing each of the bulk water and the biofilms in three of the studied ICUs. Taxonomic classification and comparison of different genera between samples highlighted the dominance of Aquabacterium (80%) and Novosphingobium (72%) in bulk water while biofilms harbored different bacteria affiliated to Pelomonas (97%) and Caulobacter (96%), Porphyrobacter (78%) and Staphylococcus (74%). Staphylococcus aureus was the only possible pathogen found with low percentage (2.32%) in three of the ICUs' biofilm and only in one of the ICU's bulk water. This study sheds light on the prevalence of unculturable bacterial flora in the biofilm ignored by the microbiological standard methods. This study was performed on tap and bulk water from ICUs; however, it indicates the need for further studies to investigate the function and activity of the microbial diversity in order to assess the real risk presented by this water microflora on patients' health.


Assuntos
Biofilmes , Água Potável/microbiologia , Unidades de Terapia Intensiva , Microbiologia da Água , Bactérias , Monitoramento Ambiental , Humanos , Metagenômica , RNA Ribossômico 16S
7.
BMC Cancer ; 18(1): 170, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426297

RESUMO

BACKGROUND: Breast cancer is considered the most common cancer in women worldwide and is the leading cause of cancer mortality. Sequences similar to Mouse Mammary Tumor Virus (MMTV) were detected in human breast cancer in several studies from different geographical areas. However, the role played by this virus in breast cancer tumorigenesis is not completely understood. These MMTV-like sequences were found to be associated with breast cancer of more malignant types. The aim of this study is to determine the prevalence of MMTV-like envelope gene (env) positivity in breast cancer and non-cancerous breast tissue from Saudi Arabia. METHODS: Detection of MMTV-like env proviral sequences was done using newly designed primers for conventional polymerase chain reaction (PCR). One hundred nighty four samples were collected from 103 females with breast cancer in addition to 51 control breast tissue obtained from individuals without cancer. We additionally investigated the association of proviral positivity with age of the patients, grade of breast cancer and presence of lymph node metastasis. The results were confirmed by sequencing. RESULTS: The prevalence of MMTV-like env proviral positivity was 8.7% (9/103). MMTV env proviral sequences were detected in 5.9% (6/101) of breast cancer tissues and 9.7% (9/93) of non-cancerous adjacent tissues obtained from the same patients. None of the 51 control sample showed positive result for the MMTV env gene. No significant association was found between detection of the virus and the age of the patient, grade of the cancer or presence of metastasis. CONCLUSION: We document the presence of low frequency of MMTV env provirus sequence among breast cancer patients from Saudi Arabia. Further studies are needed to explore the role of the MMTV in breast cancer.


Assuntos
Neoplasias da Mama/virologia , Infecções por Retroviridae/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Feminino , Humanos , Vírus do Tumor Mamário do Camundongo , Prevalência , Estudos Retrospectivos , Arábia Saudita/epidemiologia
8.
Ann Clin Microbiol Antimicrob ; 17(1): 7, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29544544

RESUMO

BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) constitutes a major global health concern causing hospital and community acquired infections. A wide diversity of MRSA genotypes are circulating in geographically related regions. Therefore understanding the molecular epidemiology of MRSA is fundamental to design control and clearance measures. METHODS: A total of 106 MRSA isolates from infection (51) and carrier colonization sites (55) are characterized genetically based on SCCmec and MLST genotyping methods in addition to detection of PVL, TSST-1 and enterotoxins. RESULTS: Sccmec-IV was the most frequently detected genotype (77.3%) followed by genotype V (13.2%) and III (9.4%). SCCmec-IVa was more prevalent among the carrier group (p value 0.002). CC80 was the most commonly identified clonal complex (CC). CC6 and CC22 were significantly more prevalent among the carrier group (p value 0.02 and 0.01, respectively). PVL was highly prevalent among the isolates (58.5%). PVL was detected in 70.6% of isolates from infection sites and 47.3% of isolates from carriers. All strains were sensitive to vancomycin, however, MRSA strains isolated from infection sites had significantly higher MICs compared to strains isolated from carrier colonization sites (p value 0.021). Five new sequence types mainly from the carrier group were identified and described in the study. CONCLUSIONS: MRSA population is genetically very diverse among carriers and infected individuals. With SCCmec type IV being most prevalent, this suggests a community origin of most MRSA strains. Therefore very well designed surveillance and clearance strategies should be prepared to prevent emergence and control spread of MRSA in the community.


Assuntos
Genótipo , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Epidemiologia Molecular , Infecções Estafilocócicas/microbiologia , Adulto , Alelos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Técnicas de Tipagem Bacteriana , Infecções Comunitárias Adquiridas , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , DNA Bacteriano , Farmacorresistência Bacteriana Múltipla/genética , Enterotoxinas/genética , Exotoxinas/genética , Feminino , Genes Bacterianos/genética , Humanos , Leucocidinas/genética , Masculino , Staphylococcus aureus Resistente à Meticilina/classificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Proteínas de Ligação às Penicilinas/genética , Filogenia , Infecções Estafilocócicas/epidemiologia , Superantígenos/genética
9.
Int J Mol Sci ; 19(6)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29865171

RESUMO

Several viruses are recognized as the direct or indirect causative agents of human tumors and other severe human diseases. Vascular endothelial growth factor (VEGF) is identified as a principal proangiogenic factor that enhances the production of new blood vessels from existing vascular network. Therefore, oncogenic viruses such as Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV) and non-oncogenic viruses such as herpes simplex virus (HSV-1) and dengue virus, which lack their own angiogenic factors, rely on the recruitment of cellular genes for angiogenesis in tumor progression or disease pathogenesis. This review summarizes how human viruses exploit the cellular signaling machinery to upregulate the expression of VEGF and benefit from its physiological functions for their own pathogenesis. Understanding the interplay between viruses and VEGF upregulation will pave the way to design targeted and effective therapeutic approaches for viral oncogenesis and severe diseases.


Assuntos
Antivirais/farmacologia , Regulação da Expressão Gênica , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética , Viroses/tratamento farmacológico , Animais , Antivirais/uso terapêutico , Humanos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Viroses/metabolismo
10.
Saudi J Med Med Sci ; 12(2): 182-187, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764565

RESUMO

Background: Viral infection is responsible for the majority of respiratory tract infections (RTI). This retrospective study evaluates the advantages of using the multiplex Xpert Xpress CoV-2/Flu/RSV plus kit in laboratory diagnosis of RTI caused by the most related viruses. Materials and Methods: Data were obtained from medical records between November 2021 and May 2023 for any sample tested using either the Xpert Xpress Flu/RSV kit, Xpert Xpress Flu kit, Xpert Xpress SARS-CoV-2 kit, and Xpert Xpress CoV-2/Flu/RSV plus kit. Results: Influenza virus A was detected in 8.5% (55/649) of the samples using the Flu PCR kit and in 4.9% (123/2538) using CoV-2/Flu/RSV plus kit, while influenza virus B detection rates were 3.7% (24/649) using the Flu PCR kit and 1.7% (43/2538) using the CoV-2/Flu/RSV plus kit. However, the detection rates using the two kits were comparable when evaluated for the same time period of the year. SARS-CoV-2 infections were detected in 16.9% (1545/9153) and 10.5% (266/2538) of the cases using the SARS-CoV-2 kit and CoV-2/Flu/RSV plus kits, respectively. Respiratory syncytial virus (RSV) was identified in 17.7% (66/372) of children using Flu/RSV kit; this number dropped significantly when age-targeted testing of RSV was performed due to involvements of adults. With the CoV-2/Flu/RSV plus kit, about 34% (35/103) of RSV infections detected were in patients aged >20 years; these cases would have previously been overlooked because adults are not routinely tested for RSV using the Flu/RSV kit. All coinfection cases (n = 16) were only detected with the CoV-2/Flu/RSV plus kit. Conclusion: The use of Xpert Xpress CoV-2/Flu/RSV plus kit not only results in shorter turnaround times through accurate detection of all four viruses, but also provides information on RSV infection in adults and coinfection rates.

11.
J Family Community Med ; 31(2): 133-139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800789

RESUMO

BACKGROUND: The aim of this study was to determine the distribution of rotavirus and adenovirus in pediatric patients evaluated for viral gastroenteritis in a hospital in the Eastern Province of Saudi Arabia for 22 years. MATERIALS AND METHODS: This was a retrospective study based in a secondary healthcare center in Saudi Arabia. Laboratory and demographic data were collected from hospital records for all pediatric patients (up to 14 years old) evaluated for viral gastroenteritis by rotavirus/adenovirus antigen detection kit from January 2000 to December 2022. Data were analyzed utilizing SPSS version 28.0. Categorical data were presented as frequency and percentages, whereas mean and standard deviations were computed for continuous variables. Chi-square test and t-test were used to determine statistical significance. RESULTS: The overall yields of antigen detection were 13.6% for rotavirus and 2.6% for adenovirus. Coinfection with both viruses was documented in 0.5% of the study population. Rotavirus was persistently detected in the past two decades with varying frequency, but the detection of adenovirus showed intervals of at least three consecutive years of zero confirmed cases. Before 2013, when the rotavirus vaccine was introduced in Saudi Arabia, rotavirus was much more prevalent than adenovirus (30% compared to 3.8% in 2010), but they became equally prevalent a decade after the introduction of the vaccine. Rotavirus gastroenteritis showed three different peaks in the year, in March, July, and December. Each peak was followed by a gradual decrease in prevalence before the next peak. Adenovirus, in contrast, was detected consistently around the year at rates between 2% and 5%. CONCLUSION: Rotavirus and adenovirus gastroenteritis have changed in prevalence in the past two decades. We found distinct seasonal patterns associated with rotavirus and adenovirus gastroenteritis. The utilization of virological testing for pediatric gastroenteritis with syndromic testing panels is to be encouraged to improve the knowledge of the true prevalence of enteric viruses.

12.
Emerg Infect Dis ; 19(12): 2034-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24274664

RESUMO

We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Infecções por Coronavirus/transmissão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arábia Saudita/epidemiologia , Estudos Soroepidemiológicos , Adulto Jovem
13.
J Virol ; 86(3): 1883-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22090125

RESUMO

The latent nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is required for the replication and partitioning of latent viral genomes. It contains an extended internal repeat (IR) region whose function is only incompletely understood. We constructed KSHV genomes lacking either LANA (KSHV-ΔLANA) or the IR region of LANA (KSHV-LANAΔ329-931). Although still capable of replicating a plasmid containing a latent origin of replication, LANAΔ329-931 does not support the establishment of stable cell lines containing a KSHV genome. These findings suggest a role for the LANA IR in KSHV episomal maintenance without its being required for replication.


Assuntos
Antígenos Nucleares/imunologia , Antígenos Virais/imunologia , Herpesvirus Humano 8/imunologia , Plasmídeos/metabolismo , Genoma Viral , Herpesvirus Humano 8/genética
14.
J Med Microbiol ; 72(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36763078

RESUMO

Introduction. Using rapid antigen diagnostic tests (RADTs) in clinical practice has shown excellent specificity but often has diminished sensitivity.Gap Statement. Local data for evaluating the diagnostic performance of a new fluorescence-based RADT and its influence on the antibiotic prescription rate are not available.Aim. To evaluate the accuracy of fluorescent immunoassay (FIA)-RADTs for diagnosing group A streptococcal (GAS) pharyngitis among children and its estimated effect as a point of care test (POCT) on the antibiotic prescription rate at the paediatric emergency department.Methodology. A prospective study was conducted, comprising children 3 to 14 years old presenting with pharyngitis. Throat swab culture and FIA-RADTs were performed on all samples. Conventional PCR was performed on the discordant samples.Results. A total of 246 children were included in this study. The sensitivity, specificity, and positive and negative predictive values of the FIA-RADT, based on culture results and PCR detection combined, were 95.6, 96.8, 94.6 and 97.4 %, respectively. Antibiotics have been prescribed to 162 (65.9 %) children; however, if FIA-RADTs had been added in the clinical practice as a POCT, only 92 (37.4 %) children would have received antibiotics in total. Additionally, implementation of FIA-RADTs would significantly reduce the antibiotic prescription rate from 48.8 and 60.6 % to 9.5 and 31.9 % among patients with clinical scores of 2 and 3, respectively.Conclusion. The new FIA-RADT is simple, prompt and reliable. It is helpful in clinical settings and may be used to reduce antibiotic overprescription, especially for children who have a low risk for GAS pharyngitis, according to the clinical score.


Assuntos
Faringite , Infecções Estreptocócicas , Criança , Humanos , Pré-Escolar , Adolescente , Antibacterianos/uso terapêutico , Estudos Prospectivos , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Sensibilidade e Especificidade , Antígenos de Bactérias , Streptococcus pyogenes , Faringite/diagnóstico , Faringite/tratamento farmacológico , Prescrições , Serviço Hospitalar de Emergência
15.
J Virol ; 85(19): 10375-88, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21795355

RESUMO

Kaposi's sarcoma herpesvirus (KSHV) Fas-associated death domain (FADD)-like interleukin-1 beta-converting enzyme (FLICE)-inhibitory protein, vFLIP, has antiapoptotic properties, is a potent activator of the NF-κB pathway, and induces the formation of endothelial spindle cells, the hallmark of Kaposi's sarcoma, when overexpressed in primary endothelial cells. We used a reverse genetics approach to study several functions of KSHV vFLIP in the context of the whole viral genome. Deletion of the gene encoding vFLIP from a KSHV genome cloned in a bacterial artificial chromosome (BAC) reduced the ability of the virus to persist and induce spindle cell formation in primary human umbilical vein endothelial cells (HUVECs). Only a few, mainly interferon (IFN)-responsive, genes were expressed in wild-type KSHV (KSHV-wt)-infected endothelial cells at levels higher than those in KSHV-ΔFLIP-infected endothelial cells, in contrast to the plethora of cellular genes induced by overexpressed vFLIP. In keeping with this observation, vFLIP induces the phosphorylation of STAT1 and STAT2 in an NF-κB-dependent manner in endothelial cells. vFLIP-dependent phosphorylation of STAT1 and STAT2 could be demonstrated after endothelial cells were infected with KSHV-wt, KSHV-ΔFLIP, and a KSHV-vFLIP revertant virus. These findings document the impact of KSHV vFLIP on the transcriptome of primary endothelial cells during viral persistence and highlight the role of vFLIP in the activation of STAT1/STAT2 and STAT-responsive cellular genes by KSHV.


Assuntos
Células Endoteliais/virologia , Herpesvirus Humano 8/patogenicidade , Fator de Transcrição STAT1/metabolismo , Proteínas Virais/metabolismo , Fatores de Virulência/metabolismo , Células Cultivadas , Deleção de Genes , Interações Hospedeiro-Patógeno , Humanos , NF-kappa B/metabolismo , Fosforilação , Fator de Transcrição STAT2/metabolismo , Proteínas Virais/genética , Fatores de Virulência/genética
16.
Saudi Med J ; 43(10): 1128-1135, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36261204

RESUMO

OBJECTIVES: To describe the frequency of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) virulence genes and clarithromycin resistance-associated mutations among Helicobacter pylori (H. pylori) clinical isolates from Eastern Saudi Arabia. METHODS: A cross-sectional study was carried out between July 2020 and June 2021 in a tertiary hospital in AL-Khobar, Saudi Arabia. A total of 34 H. pylori isolates were obtained from gastric biopsies of patients with dyspepsia. The existence of the virulence genes was studied by polymerase chain reaction and the gene fragment of the 23s ribosomal subunit (23s rRNA) gene was sequenced. RESULTS: All isolates harbored the CagA gene. Approximately 97.1% (33/34) isolates were positive using the VacA M primer and 91.2% (31/34) isolates were positive using the VacA S primer. The most frequent allelic combination was S2/M2/cag (60%), followed by S1/M2/cag (26.7%), S1/M1/cag (10%), and S2/M1/cag (3.3%). Approximately 6.5% isolates harbored the A2142G mutation and 29% isolates harbored the A2143G mutation. One isolate contained the mutation T2182C. The phylogenetic analysis showed that 58% isolates clustered with the regional and global isolates while the remaining 42% isolates seemed to be specifically circulating in Saudi Arabia. Most of the patients (73.5%) had already underwent a previous H. pylori eradication therapy. CONCLUSION: We showed that there is a regional variation in the frequency of the virulence genes among H. pylori isolates. Additionally, we showed the frequency of 23s rRNA mutations related to clarithromycin resistance in Saudi Arabia.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/genética , Claritromicina/farmacologia , Claritromicina/uso terapêutico , RNA Ribossômico 23S/genética , Infecções por Helicobacter/tratamento farmacológico , Estudos Transversais , Filogenia , Arábia Saudita , Antígenos de Bactérias/genética , Antígenos de Bactérias/uso terapêutico , Farmacorresistência Bacteriana/genética , Proteínas de Bactérias/genética , Citotoxinas/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Genótipo
17.
PLoS One ; 17(4): e0266603, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35413090

RESUMO

Most of the cases of Middle East respiratory syndrome coronavirus (MERS-CoV) were reported in Saudi Arabia. Dipeptidyl peptidase-4 (DPP4) was identified as the receptor for the virus. The level of soluble DPP4 (sDPP4) was found to be reduced in MERS-CoV infected patients while high levels of sDPP4 were suggested to be protective against MERS-CoV in animal models. We investigated whether the Saudi population has lower levels of sDPP4 which makes them more susceptible to MERS-CoV infection and, therefore, could explain the larger number of cases from the country. Blood samples were collected from 219 Saudi blood donors and 200 blood donors from other ethnic groups. The plasma level of sDPP4 was measured by ELISA and the following SNPs in the DPP4 gene; rs35128070, rs1861978, rs79700168, and rs17574, were genotyped by TaqMan SNP genotyping assay. The average level of plasma sDDP4 was significantly lower in Saudis than other Arabs and non-Arabs (P value 0.0003 and 0.012, respectively). The genotypes AG of rs35128070 and GT of rs1861978 were significantly associated with lower sDPP4 among Saudis (P value 0.002 for each). While both genotypes AA and AG of rs79700168 and rs17574 were associated with significantly lower average sDPP4 level in Saudis compared to other ethnic groups (P value 0.031 and 0.032, and 0.027 and 0.014, respectively). Herein, we report that the Saudi population has lower levels of plasma sDPP4 than other ethnic groups, which is associated with genetic variants in the DPP4 gene. This may have contributed to increase the susceptibility of the Saudi population to MERS-CoV infection and could be a factor in the long-lasting persistence of the virus in the country.


Assuntos
Infecções por Coronavirus , Dipeptidil Peptidase 4 , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Dipeptidil Peptidase 4/sangue , Suscetibilidade a Doenças , Doenças Endêmicas , Humanos , Fatores de Risco , Arábia Saudita/epidemiologia
18.
Int J Gen Med ; 15: 3605-3611, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401012

RESUMO

Introduction: Rubella is considered one of the most serious and most common congenital infections. Despite global efforts for elimination, rubella cases are still being reported in many parts of the world. The purpose of this study is to determine the level of immunity to rubella in the community and most importantly among women at childbearing age in the eastern province of Saudi Arabia and compare it with the target set by the World Health Organization (WHO) along with the incidence of acute rubella infection and the associated congenital rubella infection and congenital rubella syndrome. Methods: This is a retrospective cross-sectional study over the six years period (Jan 2014-Jun 2020) on all individuals tested for rubella IgM and IgG in a university teaching hospital. Results: Nighty one percent (15,894/17,469) of the population tested showed evidence of rubella immunity with 8.8% (1546/17,469) being susceptible. Among women at childbearing age, susceptibility to rubella was higher with 9.2% (1220/13,278) of women showing no evidence of immunity. In addition, acute rubella infection was reported for 0.17% (29/17,469) of the population tested and 0.15% (20/13,278) in women at childbearing age. No cases of congenital rubella infection were reported in the study period. Discussion: The level of Rubella immunity in the population is 91% and is less than the WHO target for rubella control therefore, risk of resurge of cases is present, indicating the need for continued national surveillance and more efforts to improve vaccination coverage in the kingdom.

19.
Ger Med Sci ; 19: Doc06, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34108851

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has circulated throughout the world causing the worst pandemic since 1918. All efforts have been marshalled towards testing different treatment approaches, obtaining clinical and epidemiological information, developing suitable diagnostic tests, and developing new vaccines. New ribonucleic acid (RNA)-based and viral vector-based vaccines have been developed and licensed under emergency use in many countries; however, there is a huge demand for vaccines, and it will take some time before a sufficient number of people are vaccinated to stop the circulation of the virus. Therefore, the proper diagnosis and identification of infected individuals are crucial for the isolation and treatment of these patients and tracing of their contacts. Many diagnostic tests and diag-nostic kits have been developed in a relatively short time. This review summarizes the principles of the available laboratory assays that are in use for the detection of SARS-CoV-2 RNA, antigens, or antibodies.


Assuntos
Teste para COVID-19 , SARS-CoV-2/isolamento & purificação , Humanos , Testes Imunológicos , Técnicas de Diagnóstico Molecular , Testes Imediatos , Reação em Cadeia da Polimerase
20.
Infect Drug Resist ; 14: 5595-5601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992386

RESUMO

PURPOSE: This study was designed to investigate the seroprevalence of WNV antibodies in humans, horses, and pigeons in the Eastern Province of Saudi Arabia. MATERIALS AND METHODS: Blood samples were collected from 323 humans, 147 horses, and 282 pigeons from two regions, Al-Ahsa and Al-Qatif, in East of Saudi Arabia. Serum samples were tested for anti-WNV antibodies by ELISA. RESULTS: The percentage of anti-WNV antibodies in the human population was found to be 9.6% (3.1% in females and 6.5% in males). This percentage was much higher in horses, as 71.4% (105/147) of the horses had anti-WNV antibodies. However, no statistically significant difference in the anti-WNV antibody prevalence was found among horses from the two regions, Al-Ahsa (73.9%) and Al-Qatif (70.3%) (P value 0.665, 95% CI 0.37-1.82). No significant difference was found in the frequency of WNV antibodies among different age groups from humans or horses. Noticeably, 72.7% of the horses had detectable anti-WNV antibodies by the age of 1 year. In total, 53.19% (150/282) of the pigeons in the study had anti-WNV antibodies. CONCLUSION: Our study provided the first evidence for anti-WNV antibody detection in humans and pigeons. This study further ascertained the high seroprevalence of the virus in horses as reported previously by Hemida et al 2019. Overall data indicates that WNV is endemic in Saudi Arabia. These findings suggest that more attention should be given to the diagnosis and reporting of WNV infections in human and animals and monitoring of virus circulation in the environment.

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