MCMV interferiert mit der MHC-Klasse-I-Antigenpräsentation

Das Zytomegalievirus der Maus (MCMV) zählt zur Familie der Herpesviridae und hat verschiedene Strategien entwickelt, um dem Immunsystem des Wirts zu entgehen. Einer dieser Mechanismen beeinflusst die Antigenpräsentation durch MHC-Klasse-I-Moleküle und wird durch das virale Genprodukt von m152 vermittelt. Dieses kodiert für ein Glykoprotein von 40 kDa Größe und wird in dieser Arbeit m152/gp40 genannt. M152/gp40 blockiert den Transport von MHC-Klasse-I-Molekülen zur Zelloberfläche und erkennt nur Moleküle der Maus, nicht aber des Menschen. Diese speziesspezifische Erkennung von MHC-Klasse-IMolekülen ist bisher nur für m152/gp40 bekannt und es wurden daher in der vorliegenden Arbeit Eigenschaften von MHC-Klasse-I-Molekülen untersucht, welche diese Speziesspezifität begründen. Es konnte gezeigt werden, dass die Spezies des gebundenen ß2- Mikroglobulins, sowie die Anzahl der Glykosylierungen der schweren Kette keinen Einfluss auf die Erkennung von MHC-Klasse-I-Antigenen durch m152/gp40 haben. Die Eigenschaft von m152/gp40, MHC-Klasse-I-Moleküle des Menschen nicht zurückzuhalten, wurde genutzt, um mit Hilfe chimärer MHC-Klasse-I-Moleküle den Bereich, der von m152/gp40 erkannt wird, einzugrenzen. Dieser liegt hauptsächlich in der a1-Domäne, weil die a2- Domäne nur eine schwache Retention bewirkt. Zwar können MHC-Klasse-I-Moleküle, die nur den luminalen Bereich umfassen, von m152/gp40 zurückgehalten werden, doch akkumulieren diese im ER und nicht im „ER-Golgi intermediate compartment“ (ERGIC) / cis-Golgi, wie Wildtyp-H-2Kb. Es wird diskutiert, ob dies ein Hinweis auf einen aktiven Transportmechanismus von MHC-Klasse-I-Molekülen aus dem ER ins ERGIC ist. Neben der Untersuchung der Funktion von m152/gp40 aufgrund der Expression des Gens allein, wurde der Einfluss der drei viralen Genprodukte von m04, m06 und m152 auf die MHC-Klasse-I-Oberflächenexpression mit Hilfe von MCMV-Deletionsmutanten untersucht. Anhand der Analyse der Oberflächenexpression verschiedener MHC-Klasse-I-Allele nach Infektion mit Wildtyp-MCMV oder MCMV-Mutanten konnte gezeigt werden, dass in MCMV nur m06/gp48 und m152/gp40 die Oberflächenexpression von MHC-Klasse-IMolekülen reduzieren. Von den untersuchten Allelen werden H-2Kb und H-2Kk nur schwach zurückgehalten. Es wurde gezeigt, dass dies auf die Funktion von m04/gp34 zurückzuführen ist, wobei m04/gp34 generell die Funktion von m152/gp40 und kaum die Funktion von m06/gp48 behindert. Für weitere Allele konnte gezeigt werden, dass diese unterschiedlich stark von den einzelnen viralen Proteinen zurückgehalten werden. So wird H-2Dd nur von m06/gp48 und m152/gp40 gemeinsam gut zurückgehalten, wohingegen H-2Db von m152/gp40 alleine gut zurückgehalten wird. Eine mögliche Rolle der unterschiedlichen Oberflächenexpression von MHC-Klasse-I-Allelen nach MCMV-Infektion für die Inhibition von NK-Zellen wird diskutiert

Major Histocompatibility Complex Class I Allele-specific Cooperative and Competitive Interactions between Immune Evasion Proteins of Cytomegalovirus

Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses with deletions of the three genes in all seven possible combinations. Surface expression of a set of MHC class I molecules specified by haplotypes H-2d (Kd, Dd, and Ld) and H-2b (Kb and Db) was the parameter for evaluation of the interference with class I trafficking. The data show the following: first, there exists no additional MCMV gene of major influence on MHC class I surface expression; second, the strength of the inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third, the immunoevasins act not only synergistically but can, in certain combinations, interact antagonistically. In essence, this work highlights the importance of studying the immunosubversive mechanisms of cytomegaloviruses in the context of gene expression during the viral replicative cycle in infected cells

Traumatic Life Events and Association With Depression, Anxiety, and Somatization Symptoms in Female Refugees

Moran JK, Jesuthasan J, Schalinski I, et al. Traumatic Life Events and Association With Depression, Anxiety, and Somatization Symptoms in Female Refugees. JAMA Network Open . 2023;6(7): e2324511.Key Points Question Which traumatic life events are associated with current depression, anxiety, and somatization symptoms in female refugees seeking psychological help? Findings In this cross-sectional study of 620 female refugees, by use of random forest regression, family violence had the highest scores associated with depression, anxiety, and somatization, beyond cumulative trauma exposure. These scores were higher than those for more frequently reported traumatic events, such as war, accident, lack of housing, hunger, and near death. Meaning These findings suggest that even for women with a history of multiple traumatic experiences, understanding the impact and likelihood of family violence is vital in diagnostic assessments and informing treatment strategies. This cross-sectional study examines which traumatic life events are associated with depression, anxiety, and somatization symptoms, beyond cumulative trauma exposure, in a sample of female refugees. Importance Different types of traumatic life events have varying impacts on symptoms of depression, anxiety, and somatization. For women from areas of the world experiencing war and humanitarian crises, who have experienced cumulative trauma exposure during war and forced migration, it is not known whether cumulative trauma or particular events have the greatest impact on symptoms. Objective To examine which traumatic life events are associated with depression, anxiety, and somatization symptoms, compared with the cumulative amount, in a sample of female refugees. Design, Setting, and Participants For this cross-sectional study, data were collected in 2016 as a part of The Study on Female Refugees. The current analysis was conducted in 2022 to 2023. This multicenter study covered 5 provinces in Germany. Participants were recruited at reception centers for refugees. Women volunteered to participate and to be interviewed after information seminars at the different centers. Exposure Traumatic life events experienced by refugees from areas of the world experiencing war and humanitarian crises. Main Outcomes and Measures Demographic variables (age, country of origin, religion, education, relationship status, and children), traumatic and adverse life events, and self-reported depression, anxiety, and somatization symptoms were measured. Random forest regressions simultaneously examined the importance of these variables on symptom scores. Follow-up exploratory mediation models tested potential associative pathways between the identified variables of importance. Results For the final sample of 620 refugee women (mean [SD] age, 32.34 [10.35] years), family violence was most associated with depression (mean [SD] variable of importance [VIM], 2.93 [0.09]), anxiety (mean [SD] VIM, 4.15 [0.11]), and somatization (mean [SD] VIM, 3.99 [0.15]), even though it was less common than other traumatic experiences, including war, accidents, hunger, or lack of housing. Other factors, such as childhood sexual abuse, injury, near-death experiences, and lack of access to health care, were also important. Follow-up analyses showed partial mediation effects between these factors in their association with symptoms, supporting the unique importance of family violence in understanding mental health. Conclusions and Relevance The findings of this cross-sectional study of refugee women who experienced multiple severe traumas related to war in their home countries and danger encountered during their migration suggest that family violence was key to their current mental health problems. Culturally sensitive assessment and treatment need to place special emphasis on these family dynamics

Near-death experiences, attacks by family members, and absence of health care in their home countries affect the quality of life of refugee women in Germany: a multi-region, cross-sectional, gender-sensitive study

Jesuthasan J, Sönmez E, Abels I, et al. Near-death experiences, attacks by family members, and absence of health care in their home countries affect the quality of life of refugee women in Germany: a multi-region, cross-sectional, gender-sensitive study. BMC Medicine. 2018;16(1): 15

Le Peuple : organe quotidien du syndicalisme

22 avril 19311931/04/22 (A11,N3751)-1931/04/22

Additional file 5: Table S5. of Near-death experiences, attacks by family members, and absence of health care in their home countries affect the quality of life of refugee women in Germany: a multi-region, cross-sectional, gender-sensitive study

Association between sociodemographic variables, quality of life, health perception, and need satisfaction. (DOCX 13 kb

Phase curve and geometric albedo of WASP-43b measured with CHEOPS, TESS, and HST WFC3/UVIS

Context. Observations of the phase curves and secondary eclipses of extrasolar planets provide a window onto the composition and thermal structure of the planetary atmospheres. For example, the photometric observations of secondary eclipses lead to the measurement of the planetary geometric albedo, Ag, which is an indicator of the presence of clouds in the atmosphere. Aims. In this work, we aim to measure the Ag in the optical domain of WASP-43b, a moderately irradiated giant planet with an equilibrium temperature of ~1400 K. Methods. For this purpose, we analyzed the secondary eclipse light curves collected by CHEOPS together with TESS along with observations of the system and the publicly available photometry obtained with HST WFC3/UVIS. We also analyzed the archival infrared observations of the eclipses and retrieve the thermal emission spectrum of the planet. By extrapolating the thermal spectrum to the optical bands, we corrected for the optical eclipses for thermal emission and derived the optical Ag. Results. The fit of the optical data leads to a marginal detection of the phase-curve signal, characterized by an amplitude of 160 ± 60 ppm and 80a-? 50+60 ppm in the CHEOPS and TESS passbands, respectively, with an eastward phase shift of ~50 (1.5Ï ? detection). The analysis of the infrared data suggests a non-inverted thermal profile and solar-like metallicity. The combination of the optical and infrared analyses allows us to derive an upper limit for the optical albedo of Ag< 0.087, with a confidence of 99.9%. Conclusions. Our analysis of the atmosphere of WASP-43b places this planet in the sample of irradiated hot Jupiters, with monotonic temperature-pressure profile and no indication of condensation of reflective clouds on the planetary dayside.ISSN:0004-6361ISSN:1432-074

Additional file 4: Table S4. of Near-death experiences, attacks by family members, and absence of health care in their home countries affect the quality of life of refugee women in Germany: a multi-region, cross-sectional, gender-sensitive study

Type of support on flight. (DOCX 14 kb