Browsing by Author "Onder, Sevgen"

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Association of Class II Human Leukocyte Antigen (Hla) Alleles with Pulmonary Sarcoidosis
(2018) Esendagli, Dorina; Ozmen, Fusun; Koksal, Deniz; Onder, Sevgen; Emri, Salih; https://orcid.org/0000-0002-6619-2952; https://orcid.org/0000-0001-8374-3691; 32476894; ABF-9398-2020; ABE-1458-2020
Background and objectives: Sarcoidosis is a systemic inflammatory disease of unknown etiology that involves any part of the body, mainly the lungs and thoracic lymph nodes. The clinical presentation is heterogeneous based on the degree and extent of organ involvement. The existence of variable clinical presentations and treatment responses suggest an important role of genetic predisposition. In genetic studies, sarcoidosis was found to be associated with several genes, but the strongest link was with HLA region. The aim of this study was to investigate the association of HLA class II alleles with the extent and course of disease in Turkish patients with sarcoidosis. Methods: The study included 103 patients with sarcoidosis and 100 unrelated healthy controls. HLA-DRB1 and HLA-DQB1 typing was performed by using Polymerase Chain Reaction-Sequence Specific Priming ( PCR-SSP) method at low resolution level. Results: HLA-DRB1* and -DQB1* analysis revealed that while the frequency of HLA-DRB1* 01 was significantly higher in the control group, HLA-DRB1* 13 and -DQB1* 06 alleles were more frequent in the sarcoidosis patients. When the patients were grouped based on clinical outcome as remitters and non-remitters, HLA-DRB1* 10 allele was only detected in the remitters, whereas the frequency of HLA-DQB1* 06 allele was significantly higher in non-remitters. Conclusions: This study supported the association of HLA alleles with sarcoidosis. In a considerably high number of patients with Turkish origin, the frequency of HLA-DRB1* 13, -DRB1* 10 and HLA-DQB1* 06 alleles was significantly associated with increased risk and clinical outcome.
Characterization of local SARS-CoV-2 isolates and pathogenicity in IFNAR(-/-) mice
(2020) Hanifehnezhad, Alireza; Kehribar, Ebru Sahin; Oztop, Sidika; Sheraz, Ali; Kasirga, Serkan; Ergunay, Koray; Onder, Sevgen; Yilmaz, Erkan; Engin, Doruk; Oguzoglu, T. Cigdem; Seker, Urartu Ozgur Safak; Yilmaz, Engin; Ozkul, Aykut; 0000-0001-5653-6080; 33015402; AAJ-7911-2020
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently a global pandemic with unprecedented public health, economic and social impact. The development of effective mitigation strategies, therapeutics and vaccines relies on detailed genomic and biological characterization of the regional viruses. This study was carried out to isolate SARS-CoV-2 viruses circulating in Anatolia, and to investigate virus propagation in frequently-used cells and experimental animals. We obtained two SARS-CoV-2 viruses from nasopharngeal swabs of confirmed cases in Vero E6 cells, visualized the virions using atomic force and scanning electron microscopy and determined size distribution of the particles. Viral cytopathic effects on Vero E6 cells were initially observed at 72 h post-inoculation and reached 90% of the cells on the 5th day. The isolates displayed with similar infectivity titers, time course and infectious progeny yields. Genome sequencing revealed the viruses to be well-conserved, with less than 1% diversity compared to the prototype virus. The analysis of the viral genomes, along with the available 62 complete genomes from Anatolia, showed limited diversity (up to 0.2% on deduced amino acids) and no evidence of recombination. The most prominent sequence variation was observed on the spike protein, resulting in the substitution D614G, with a prevalence of 56.2%. The isolates produced non-fatal infection in the transgenic type I interferon knockout (IFNAR(-/-)) mice, with varying neutralizing antibody titers. Hyperemia, regional consolidation and subpleural air accumulation was observed on necropsy, with similar histopathological and immunohistochemistry findings in the lungs, heart, stomach, intestines, liver, spleen and kidneys. Peak viral loads were detected in the lungs, with virus RNA present in the kidneys, jejunum, liver, spleen and heart. In conclusion, we characterized two local isolates, investigated in vitro growth dynamics in Vero E6 cells and identified IFNAR-/- mice as a potential animal model for SARS-CoV-2 experiments.
A Highly Potent SARS-CoV-2 Blocking Lectin Protein
(2022) Ahan, Recep E.; Hanifehnezhad, Alireza; Kehribar, Ebru S.; Oguzoglu, Tuba C.; Foldes, Katalin; Ozcelik, Cemile E.; Filazi, Nazlican; Oztop, Sidika; Palaz, Fahreddin; Onder, Sevgen; Bozkurt, Eray U.; Ergunay, Koray; Ozkul, Aykut; Seker, Urartu Ozgur Safak; https://orcid.org/0000-0001-5653-6080; 35426678; AAJ-7911-2020
The COVID-19 (coronavirus disease-19) pandemic affected more than 180 million people around the globe, causing more than five million deaths as of January 2022. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus, has been identified as the primary cause of the infection. The number of vaccinated people is increasing; however, prophylactic drugs are highly demanded to ensure secure social contact. A number of drug molecules have been repurposed to fight against SARS-CoV-2, and some of them have been proven to be effective in preventing hospitalization or ICU admissions. Here, we demonstrated griffithsin (GRFT), a lectin protein, to block the entry of SARS-CoV-2 and its variants, Delta and Omicron, into the Vero E6 cell lines and IFNAR(-/-) mouse models by attaching to the spike protein of SARS-CoV-2. Given the current mutation frequency of SARS-CoV-2, we believe that GRFT protein-based drugs will have a high impact in preventing the transmission of both the Wuhan strain as well as any other emerging variants, including Delta and Omicron variants, causing the high-speed spread of COVID-19.