Downregulation of MHC class I expression by influenza A and B viruses

Manipulation of the MHC-I presentation pathway, and thus limiting MHC-I cell surface expression, is used by many viruses to evade immune recognition. In particular, downregulation of MHC-I molecules at the cell surface can reduce the ability of CD8+ T cells to recognize viral peptides presented by MHC-I molecules and thereby delay viral clearance by CD8+ T cells. To date, MHC-I downregulation by influenza viruses has not been reported. Given that influenza virus infections are a global health concern and that CD8+ T cells play an important role in promoting influenza virus clearance and recovery from influenza disease, we investigated whether influenza A and B viruses (IAV, IBV) downregulated MHC-I as a novel mechanism to evade cellular immunity. Here, we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection in vitro. This observation was consistent across a panel of class I-reduced (C1R) cell lines expressing 14 different HLA-A or -B alleles and a panel of 721.221 cell lines expressing 11 HLA-C alleles. Interestingly, IBV infection caused more pronounced reduction in surface MHC-I expression compared to IAV. Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation. Our data demonstrated that while IAV caused a global loss of MHC-I within influenza-infected cells, IBV infection resulted in the preferential loss of MHC-I molecules from the cell surface, consequent of delayed MHC-I trafficking to the cell surface, resulting from retaining MHC-I intracellularly during IBV infection. Overall, our study suggests that influenza viruses across both IAV and IBV subtypes have the potential to downregulate MHC-I surface expression levels. Our findings provide new insights into the host-pathogen interaction of influenza A and B viruses and inform the design of novel vaccine strategies against influenza viruses

Downregulation of MHC Class I Expression by Influenza A and B Viruses

Manipulation of the MHC-I presentation pathway, and thus limiting MHC-I cell surface expression, is used by many viruses to evade immune recognition. In particular, downregulation of MHC-I molecules at the cell surface can reduce the ability of CD8+ T cells to recognize viral peptides presented by MHC-I molecules and thereby delay viral clearance by CD8+ T cells. To date, MHC-I downregulation by influenza viruses has not been reported. Given that influenza virus infections are a global health concern and that CD8+ T cells play an important role in promoting influenza virus clearance and recovery from influenza disease, we investigated whether influenza A and B viruses (IAV, IBV) downregulated MHC-I as a novel mechanism to evade cellular immunity. Here, we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection in vitro. This observation was consistent across a panel of class I-reduced (C1R) cell lines expressing 14 different HLA-A or -B alleles and a panel of 721.221 cell lines expressing 11 HLA-C alleles. Interestingly, IBV infection caused more pronounced reduction in surface MHC-I expression compared to IAV. Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation. Our data demonstrated that while IAV caused a global loss of MHC-I within influenza-infected cells, IBV infection resulted in the preferential loss of MHC-I molecules from the cell surface, consequent of delayed MHC-I trafficking to the cell surface, resulting from retaining MHC-I intracellularly during IBV infection. Overall, our study suggests that influenza viruses across both IAV and IBV subtypes have the potential to downregulate MHC-I surface expression levels. Our findings provide new insights into the host-pathogen interaction of influenza A and B viruses and inform the design of novel vaccine strategies against influenza viruses

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Determination if methicillin resistant staphylococcus aureus in ıntensive care unit, operation room and health care workers-susceptibilty of mupirocin

Çalışmada Afyon Kocatepe Üniversitesi Tıp Fakültesi Yoğun Bakım Üniteleri ve ameliyathanelerinden 37 farklı çevre örneği ile burada çalışan 18 doktor, 22 hemşire ve 26 yardımcı sağlık personeli olmak üzere top¬lam 66 hastane çalışanının el, burun kültürlerinde Metisilin Resistant Staphylococcus aureus (MRSA) araştırılmıştır. Burunda S.aureus taşıyıcılığı olan 51 (%77.3) personelden 13’ünde (%19.7) MRSA saptanmış, elde MRSA taşıyıcılığı tüm personelde % 10.6 bulunmuştur. El ve burun kültürleri birlikte değerlendirildiklerinde ise sağ¬lık çalışanlarında MRSA taşıyıcılığı %28.8 olarak saptanmıştır. Yoğun Bakım Üniteleri ve ameliyathanelerinden 37 farklı çevre örneğinden altısında (%16.2) MRSA izole edilmiş, hava örneklerinin hiçbirinde MRSA tespit edilememiştir. MRSA kolonizasyonun önlemesinde Mupirosin kullanılmaktadır. MRSATarda mupirosin direnci %5.0 olarak bulunmuştur. Geçici yada kısa süreli taşıyıcı olan yoğun bakım çalışanları hastadan hastaya MRSA geçişinde rol alabileceğinden periyodik olarak bu kişilerin MRSA yönünden taranmaları ve taşıyıcıların dekontaminasyonu gerekmektedir.In this study, 66 doctors and nurses of three intensive care units of Afyon Kocatepe University Hospital were screened for nasal and hand carriage of Methicil-lin-Resistant Staphylococcus aureus (MRSA). Of these subjects 51 (77.3%) were found to be nasal carriers of S.aureus and only 13 (19.6%) of them were found to be carriers of MRSA. Hand carriage of MRSA was detected in 10.6% doctors and nurses. Staff carriage of MRSA was found to be 28.8% when hand and nose cultures were examined together. We have also studied the possible role of contaminated environmental surfaces as a reservoir of MRSA in the same units. Among the samples collected from 37 different environmental regions from each unit, only six were found to be contaminated with MRSA (16.2%). No MRSA were detected from the air samples of the units. Decolonization with mupirocin can be used to control its dissemination. Mupirocin resistance was found 5.0% all MRSA. As transient or short term carriage of MRSA by medical staff may play an important role in the transfer of bacteria between patients, screening of staff periodically and decontamination of them in terms of MRSA should be taken into consideration in the infection control studies of MRSA

Determination if methicillin resistant staphylococcus aureus in ıntensive care unit, operation room and health care workers-susceptibilty of mupirocin

Çalışmada Afyon Kocatepe Üniversitesi Tıp Fakültesi Yoğun Bakım Üniteleri ve ameliyathanelerinden 37 farklı çevre örneği ile burada çalışan 18 doktor, 22 hemşire ve 26 yardımcı sağlık personeli olmak üzere top¬lam 66 hastane çalışanının el, burun kültürlerinde Metisilin Resistant Staphylococcus aureus (MRSA) araştırılmıştır. Burunda S.aureus taşıyıcılığı olan 51 (%77.3) personelden 13’ünde (%19.7) MRSA saptanmış, elde MRSA taşıyıcılığı tüm personelde % 10.6 bulunmuştur. El ve burun kültürleri birlikte değerlendirildiklerinde ise sağ¬lık çalışanlarında MRSA taşıyıcılığı %28.8 olarak saptanmıştır. Yoğun Bakım Üniteleri ve ameliyathanelerinden 37 farklı çevre örneğinden altısında (%16.2) MRSA izole edilmiş, hava örneklerinin hiçbirinde MRSA tespit edilememiştir. MRSA kolonizasyonun önlemesinde Mupirosin kullanılmaktadır. MRSATarda mupirosin direnci %5.0 olarak bulunmuştur. Geçici yada kısa süreli taşıyıcı olan yoğun bakım çalışanları hastadan hastaya MRSA geçişinde rol alabileceğinden periyodik olarak bu kişilerin MRSA yönünden taranmaları ve taşıyıcıların dekontaminasyonu gerekmektedir.In this study, 66 doctors and nurses of three intensive care units of Afyon Kocatepe University Hospital were screened for nasal and hand carriage of Methicil-lin-Resistant Staphylococcus aureus (MRSA). Of these subjects 51 (77.3%) were found to be nasal carriers of S.aureus and only 13 (19.6%) of them were found to be carriers of MRSA. Hand carriage of MRSA was detected in 10.6% doctors and nurses. Staff carriage of MRSA was found to be 28.8% when hand and nose cultures were examined together. We have also studied the possible role of contaminated environmental surfaces as a reservoir of MRSA in the same units. Among the samples collected from 37 different environmental regions from each unit, only six were found to be contaminated with MRSA (16.2%). No MRSA were detected from the air samples of the units. Decolonization with mupirocin can be used to control its dissemination. Mupirocin resistance was found 5.0% all MRSA. As transient or short term carriage of MRSA by medical staff may play an important role in the transfer of bacteria between patients, screening of staff periodically and decontamination of them in terms of MRSA should be taken into consideration in the infection control studies of MRSA

patients?: Turkish Oncology Group Study

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients.Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study.Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85 +/- 10.4).The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (127%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis.Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007).Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.C1 [Yildiz, Birol; Erturk, Ismail; Acar, Ramazan; Karadurmus, Nuri] Hlth Sci Univ, Gulhane Training & Res Hosp, Dept Med Oncol, Ankara, Turkey.[Kucukarda, Ahmet; Gokyer, Ali] Trakya Univ, Fac Med, Dept Med Oncol, Edirne, Turkey.[Demiray, Atike Gokcen] Pamukkale Univ, Fac Med, Dept Med Oncol, Denizli, Turkey.[Paydas, Semra] Cukurova Univ, Fac Med, Dept Med Oncol, Adana, Turkey.[Aral, Ipek Pinar] Nevsehir State Hosp, Dept Radiat Oncol, Nevsehir, Turkey.[Gumusay, Ozge] Gazi Osman Pasa Univ, Fac Med, Dept Med Oncol, Tokat, Turkey.[Bilici, Ahmet] Medipol Univ, Fac Med, Dept Med Oncol, Istanbul, Turkey.[Akdeniz, Nadiye] Dicle Univ, Fac Med, Dept Med Oncol, Diyarbakir, Turkey.[Bahceci, Aykut] Gaziantep Dr Ersin ARSLAN Training & Res Hosp, Dept Med Oncol, Gaziantep, Turkey.[Demir, Hacer] Afyon Kocatepe Univ, Fac Med, Dept Med Oncol, Afyon, Turkey.[Esin, Ece] Bayindir Hosp, Dept Med Oncol, Ankara, Turkey.[Uyeturk, Ummugul] Abant Izzet Baysal Univ, Fac Med, Dept Med Oncol, Bolu, Turkey.[Okten, Ilker Nihat] Istanbul Medeniyet Univ, Gortepe Training & Res Hosp, Dept Med Oncol, Istanbul, Turkey.[Turk, H. Mehmet] BezmiAlem Vakif Univ, Dept Med Oncol, Istanbul, Turkey.[Topaloglu, Ulas Serkan] Kayseri City Hosp, Dept Internal Med, Kayseri, Turkey.[Basoglu, Tugba] Marmara Univ, Fac Med, Dept Med Oncol, Istanbul, Turkey.[Turhal, Nazim Serdar] Anadolu Med Ctr, Dept Med Oncol, Kocaeli, Turkey.[Cinkir, Havva Yesil] Gaziantep Univ, Dept Med Oncol, Fac Med, Gaziantep, Turkey.[Menekse, Serkan; Kut, Engin] Manisa City Hosp, Dept Med Oncol, Manisa, Turkey.[Cakmak, Yagmur] Kocaeli Univ, Fac Med, Dept Med Oncol, Kocaeli, Turkey.[Urun, Yuksel] Ankara Univ, Fac Med, Dept Med Oncol, Ankara, Turkey.[Dal, Pinar] Eskisehir City Hosp, Dept Med Oncol, Eskisehir, Turkey.[Sakalar, Teoman] Kahramanmaras City Hosp, Dept Med Oncol, Kahramanmaras, Turkey.[Aktepe, Oktay Halit] Hacettepe Univ, Fac Med, Dept Med Oncol, Ankara, Turkey

Does primary tumor localization has prognostic importance in seminoma patients?: Turkish oncology Group study

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients. Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study. Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007). Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization. © 2020 Zerbinis Publications. All rights reserved