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During the analysis of a collection of Pseudomonas strains linked to an outbreak in an intensive care unit at King Faisal Specialist Hospital and Research Center in 2019, one isolate (CFS3442T) was identified phenotypically as Pseudomonas aeruginosa. However, whole-genome sequencing revealed its true identity as a member of the genus Stenotrophomonas, distinct from both P. aeruginosa and Stenotrophomonas maltophilia. The isolate demonstrated: (i) a significant phylogenetic distance from P. aeruginosa; (ii) considerable genomic differences from several S. maltophilia reference strains and other Stenotrophomonas species; and (iii) unique phenotypic characteristics. Based on the combined geno- and phenotypic data, we propose that this isolate represents a novel species within the genus Stenotrophomonas, for which the name Stenotrophomonas riyadhensis sp. nov. is proposed. The type strain is CFS3442T (=NCTC 14921T=LMG 33162T).
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Ácidos Grasos , Stenotrophomonas , Ácidos Grasos/química , Filogenia , Análisis de Secuencia de ADN , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Hibridación de Ácido Nucleico , Composición de Base , Técnicas de Tipificación Bacteriana , HospitalesRESUMEN
OBJECTIVES: Patients with chronic hepatitis B virus (HBV) may exhibit significant liver pathology despite alanine aminotransferase (ALT) and HBV DNA levels below the cutoff values advised by treatment guidelines. We evaluated candidacy for HBV therapy when baseline histopathological changes are taken into consideration. METHODS: Clinical, biochemical, serological, virological, and histopathological (METAVIR score) data of 117 patients with HBeAg-negative chronic HBV genotype D were collected and analyzed. RESULTS: Significant pathology (≥F2 and/or ≥A2) and fibrosis (≥F2 ± ≥A2) were found in 73 (62.4%) and 59 (50.4%) patients, respectively. Based on HBV DNA (>2,000 IU/ml) and ALT levels >2 × 40 U/l (the standard cutoff value), only 31 (26.5%) patients were candidates for therapy. This increased to 58 (49.6%) patients when the new ALT cutoff values (30 U/l for males, and 19 U/l for females) were applied. Relying on either ≥F2 and/or A ≥2 or ≥F2 ± ≥A2 increases the treatment candidacy to 73 (62.4%) and 59 (50.4%) patients, respectively. Also, when compared with standard ALT cutoff values, applying both new ALT cutoff values with either significant pathology or fibrosis increases treatment candidacy to 28 (23.9%) and 42 (35.9%) patients, respectively. CONCLUSION: Liver pathology is more reliable than ALT and HBV DNA in the decision to treat patients with HBeAg-negative chronic HBV genotype D.
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Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/patología , Hígado/patología , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Biopsia , Femenino , Genotipo , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/virología , Humanos , Hígado/virología , Masculino , Persona de Mediana Edad , Carga Viral , Adulto JovenRESUMEN
Interleukins (ILs) are signaling molecules that are crucial in regulating immune responses during infectious diseases. Pro-inflammatory ILs contribute to the activation and recruitment of immune cells, whereas anti-inflammatory ILs help to suppress excessive inflammation and promote tissue repair. Here, we provide a comprehensive overview of the role of pro-inflammatory and anti-inflammatory ILs in infectious diseases, with a focus on the mechanisms underlying their effects, their diagnostic and therapeutic potential, and emerging trends in IL-based therapies.
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Coronaviridae is a large family of enveloped, positive-strand RNA viruses that has plagued the world since it was discovered in humans in the 1960s. The recent severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic has already exceeded the number of combined cases and deaths witnessed during previous SARS-CoV and Middle East respiratory syndrome-CoV epidemics in the last two decades. This narrative review focuses on genomic mutations in SARS-CoV-2 and their impact on the severity and progression of COVID-19 in light of reported data in the literature. Notable SARS-CoV-2 mutations associated with open reading frames, the S glycoprotein, and nucleocapsid protein, currently circulating globally, are discussed along with emerging mutations such as those in the SARS-CoV-2 VUI 202012/01 variant in the UK and other European countries, the 484K.V2 and P.1 variants in Brazil, the B.1.617 variant in India, and South African variants 501Y.V2 and B.1.1.529 (omicron). These variants have the potential to influence the receptor binding domain, host-virus fusion, and SARS-CoV-2 replication. Correlating these mutations with disease dynamics could help us understand their pathogenicity and design appropriate therapeutics.
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COVID-19 , SARS-CoV-2 , COVID-19/genética , Humanos , Mutación/genética , Unión Proteica , SARS-CoV-2/genéticaRESUMEN
INTRODUCTION: In December 2019, a new severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China, causing coronavirus disease 2019. The present study investigated genetic profiles and variations of SARS-CoV-2 distributed in different regions of Saudi Arabia to begin to understand the pathogenesis and transmission of SARS-CoV-2 in this country and analyzed associations of these variations with host factors. METHODOLOGY: In total, 774 SARS-CoV-2 genomic sequences obtained and annotated by the Global Initiative on Sharing All Influenza Data (GISAID) were captured and analyzed. RESULTS: The most common SARS-CoV-2 clades in Saudi Arabia were GH followed by O, GR, G, and S. Statistically significant associations were detected between clades and patient outcome. Age, as a host factor, was significantly associated with many variables, including virus geographical location, clade, and patient outcome. The most common variants detected were the NSP12_P323L mutation 94.9%, followed by the D614G mutation (76%) and the NS3_Q57H mutation (71.4%). The concerned variants B.1.1.7, B.1.351, and P.1 were not detected in our population. D614G was associated with higher morbidities than the wild-type virus, including higher rates of death and hospitalization. The NS3_Q57H mutation was the only variant associated with better patient outcome than the wild type. Risk of death was highest with the NSP12_P323L mutation (OR = 1.84; 95% CI = 0.37-9.30) and lowest with the NS3_Q57H mutation (OR = 0.43; 95% CI = 0.25-0.727). CONCLUSIONS: SARS-CoV-2 has evolved uniquely and independently in Saudi Arabia. Our findings provide evidence to begin linking the evolutionary implications to host factors and their effects on the virus severity and transmission.
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COVID-19/epidemiología , SARS-CoV-2 , Adulto , Anciano , COVID-19/genética , COVID-19/transmisión , Femenino , Genoma Viral , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Pandemias , Arabia Saudita/epidemiología , Secuenciación Completa del GenomaRESUMEN
Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV). SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV. Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment. In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-ß, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line. rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding. Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity. Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines. In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF. These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner. Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
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Virus de la Influenza A/inmunología , Infecciones por Orthomyxoviridae/inmunología , Proteína D Asociada a Surfactante Pulmonar/inmunología , Células A549 , Animales , Aves , Citocinas/inmunología , Perros , Hemaglutininas/inmunología , Humanos , Células de Riñón Canino Madin Darby , Péptidos/genética , Péptidos/inmunología , Proteína D Asociada a Surfactante Pulmonar/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunologíaRESUMEN
INTRODUCTION: In early 2009, a novel influenza A (H1N1) virus appeared in Mexico and rapidly disseminated worldwide. Little is known about the phylogeny and evolutionary dynamics of the H1N1 strain found in Saudi Arabia. METHODOLOGY: Nucleotide sequencing and bioinformatics analyses were used to study molecular variation between the virus isolates. RESULTS: In this report, 72 hemagglutinin (HA) and 45 neuraminidase (NA) H1N1 virus gene sequences, isolated in 2009 from various regions of Saudi Arabia, were analyzed. Genetic characterization indicated that viruses from two different clades, 6 and 7, were circulating in the region, with clade 7, the most widely circulating H1N1 clade globally in 2009, being predominant. Sequence analysis of the HA and NA genes revealed a high degree of sequence identity with the corresponding genes from viruses circulating in the South East Asia region and with the A/California/7/2009 strain. New mutations in the HA gene of pandemic H1N1 (pH1N1) viruses, that could alter viral fitness, were identified. Relaxed-clock and Bayesian Skyline Plot analyses, based on the isolates used in this study and closely related globally representative strains, indicated marginally higher substitution rates than the type strain (5.14×10-3 and 4.18×10-3 substitutions/nucleotide/year in the HA and NA genes, respectively). CONCLUSIONS: The Saudi isolates were antigenically homogeneous and closely related to the prototype vaccine strain A/California/7/2009. The antigenic site of the HA gene had acquired novel mutations in some isolates, making continued monitoring of these viruses vital for the identification of potentially highly virulent and drug resistant variants.
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Variación Genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/virología , Neuraminidasa/genética , Filogenia , Proteínas Virales/genética , Adolescente , Adulto , Niño , Preescolar , Epítopos/genética , Femenino , Humanos , Lactante , Recién Nacido , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Masculino , Epidemiología Molecular , Mutación , Arabia Saudita/epidemiología , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family and is related to dengue, Chikungunya, West Nile, yellow fever, and Japanese encephalitis viruses. ZIKV was first discovered in Uganda in 1947. Different species of mosquito from the Aedes genus, mainly A. aegypti and A. albopictus are the vectors responsible for ZIKV infection in humans. It is also reported that ZIKV is transmitted congenitally, sexually, and through blood donation. Until recently, ZIKV outbreaks were sporadic and self-limiting. The first large epidemic was reported from Yap Island in 2007 followed by an outbreak of Zika fever in French Polynesia in 2013. Brazil is the epicenter of the current ZIKV epidemic which is rapidly spreading across the Americas. ZIKV infection remained relatively less studied in view of its low case numbers, and low clinical impact relative to other arboviruses. However, all this is set to change with its rapid spread in the Western hemisphere and suspected complications particularly microcephaly in newborn babies with ZIKV infected mothers. ZIKV is expected to substantially add to both short-term and long-term economic burden of the effected countries. Due to the large number of people travelling across the borders and some reported cases of transmission of ZIKV via contaminated blood, screening and identification of asymptomatic infected individuals are important.
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Microcefalia/epidemiología , Pandemias , Infección por el Virus Zika/epidemiología , Virus Zika/aislamiento & purificación , Aedes , Animales , Humanos , Insectos Vectores , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/transmisiónRESUMEN
INTRODUCTION: Saudi Arabia (SA) experienced a highly pathogenic avian influenza (HPAI) H5N1 outbreak in domesticated birds in 2007. METHODOLOGY: Forty-three hemagglutinin (HA) and 41 neuraminidase (NA) genes of HPAI H5N1 viruses were sequenced and phylogenetic analyses of completely sequenced genes were performed to compare with other viral HA and NA gene sequences available in the public databases. RESULTS: Molecular characterization of the H5N1 viruses revealed two genetically distinct clades, 2.2.2 and 2.3.1, of H5N1 viruses circulating in the area. Amino acid sequence analysis of the HA gene indicated that the virus from 2.2.2 contained the sequence SPQGERRRK-R/G at the cleavage site, while the virus from 2.3.1 contained the sequence SPQRERRRK-R/G. Additionally, a few mutations with amino acid substitutions such as M226I at N-link glycosylation site were identified in two of these isolates. Amino acid sequence of the NA gene showed a 20-amino-acid deletion in the NA stalk region, required for enhanced virulence of influenza viruses and its adaptation from wild birds to domestic chickens. As close contact between humans and birds is unavoidable, there is a need for a thorough understanding of the virus epidemiology, factors affecting the spread of the virus, and molecular characterization such as phylogeny and substitution rates of H5N1 viruses circulating in the region. CONCLUSION: Two genetically distinct clades were found to be circulating in the country, which could likely result in recombination and emergence of more virulent viral strains. These findings could be helpful for the authorities devising control measures against these viruses.
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Brotes de Enfermedades , Variación Genética , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/epidemiología , Gripe Aviar/virología , Animales , Análisis por Conglomerados , Genotipo , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H5N1 del Virus de la Influenza A/clasificación , Epidemiología Molecular , Neuraminidasa/genética , Filogenia , Aves de Corral , Arabia Saudita/epidemiología , Análisis de Secuencia de ADN , Proteínas Virales/genéticaRESUMEN
Although viruses that belong to the coronavirus family are known since the 1930s, they only gained public health attention when they were discovered to be the causative agent of the severe acute respiratory syndrome (SARS) outbreak in China in 2002-2003. On 22 September 2012, the Ministry of Health (MOH) in Saudi Arabia announced the detection of what was described as a "rare pattern" of coronavirus respiratory infection in three individuals, two Saudi citizens and one person from the Gulf Region. Neither Saudi citizen survived the infection. Molecular analysis of the isolates showed that the virus belongs to the genus beta-coronavirus. It is not known if the new isolates are circulating in the population or has recently diverged. The emergence of these novel isolates that resulted in fatal human infection ascertains that health authorities all over the world must be vigilant for the possibility of new global pandemics due to novel viral infection.
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Infecciones por Coronavirus/epidemiología , Coronavirus/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Análisis por Conglomerados , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Resultado Fatal , Genotipo , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/genética , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/virología , Arabia Saudita/epidemiologíaRESUMEN
INTRODUCTION: Hepatitis C virus (HCV), which is a major cause of liver diseases worldwide, undergoes genetic variation during the course of infection. The aim of this study was to examine sequence variations within the HVR1 region of HCV genotype 4 in infected Saudi patients treated with a combination therapy of interferon-α and ribavirin. METHODOLOGY: cDNA of the HVR1 region of HVC-4 from one responder and one non-responder patients was generated, cloned and sequenced. Ten clones were randomly selected and analyzed for changes in nucleotide and amino acid sequences before the start of treatment, and subsequently three and six months after the start of the therapy course. RESULTS: Based on nucleotide and amino acid sequence variations, the HVR1 region is highly sequence variable. In both the responder and the non-responder patients, amino acid sequence variations were observed and a clear distinction between patients was evident. The amino acid changes after the treatment course were different in the responder compared to the non-responder subject. Five amino acids (residues 364 to 367, 381 and 409) were unique in the non-responder patient. CONCLUSION: Considerable amino acid variations were observed in the HVR1 region in both responder and non-responder patients. These findings could have implications for the development of an HCV vaccine as well as treatment protocols for HCV infections.