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Murine leukemia virus (MLV)-presenting cells form stable intercellular contacts with target cells during infection of lymphoid tissue, indicating a role of cell-cell contacts in retrovirus dissemination. Whether host cell adhesion proteins are required for retrovirus spread in vivo remains unknown. Here, we demonstrate that the lymphocyte-function-associated-antigen-1 (LFA1) and its ligand intercellular-adhesion-molecule-1 (ICAM1) are important for cell-contact-dependent transmission of MLV between leukocytes. Infection experiments in LFA1- and ICAM1-deficient mice demonstrate a defect in MLV spread within lymph nodes. Co-culture of primary leukocytes reveals a specific requirement for ICAM1 on donor cells and LFA1 on target cells for cell-contact-dependent spread through trans- and cis-infection. Importantly, adoptive transfer experiments combined with a newly established MLV-fusion assay confirm that the directed LFA1-ICAM1 interaction is important for retrovirus fusion and transmission in vivo. Taken together, our data provide insights on how retroviruses exploit host proteins and the biology of cell-cell interactions for dissemination.

Murine leukemia virus (MLV)-presenting cells form stable intercellular contacts with target cells during infection of lymphoid tissue, indicating a role of cell-cell contacts in retrovirus dissemination. Whether host cell adhesion proteins are required for retrovirus spread in vivo remains unknown. Here, we demonstrate that the lymphocyte function-associated-antigen-1 (LFA1) and its ligand intercellular-adhesion-molecule-1 (ICAM1) are important for cell contact-dependent transmission of MLV between leukocytes. Infection experiments in LFA1- and ICAM1-deficient mice demonstrate a defect in MLV spread within lymph nodes. Co-culture of primary leukocytes reveal a specific requirement for ICAM1 on donor cells and LFA1 on target cells for cell contact-dependent spread through trans- and cis-infection. Importantly, adoptive transfer experiments combined with a newly established MLV-fusion assay confirm that the directed LFA1-ICAM1 interaction is important for retrovirus fusion and transmission in vivo. Taken together, our data provide insights how retroviruses exploit host proteins and the biology of cell-cell interactions for dissemination.

Objectives Code status specifies the action that healthcare providers should take in the event of cardiac arrest. Studies have shown, however, that patients with do-not-resuscitate/do-not-intubate (DNR/DNI) orders have worse outcomes and do not consistently receive the standard of care. Several studies have demonstrated that physicians behave differently toward patients with DNR/DNI orders, but little research exists into whether DNR/DNI status affects the practice of other members of the care team. Our objective was to determine whether code status affects decision making by nursing staff. Methods This was an anonymous, self-administered survey of nurses between April 2018 and March 2019 using SurveyMonkey. The survey contained four previously published clinical vignettes followed by a series of questions regarding specific interventions tailored to reflect nursing escalation of care. Our focus was two local hospitals: one large academic quaternary-referral center and one large community hospital. Registered nurses on medical-surgical units identified based on available unit-specific e-mail listservs from both hospitals were the participants. Nurses in higher-acuity units were excluded. Results Nurses are significantly less likely to call rapid response or a physician when a patient undergoes certain changes in clinical status if the patient is labeled as DNR/DNI rather than full code. For all of the vignettes, respondents were less likely to say they would call rapid response or a physician for patients with a DNR/DNI status who developed tachycardia (P 0.05). Nurses with >3 years of experience were less likely to escalate care throughout the vignettes (odds ratio Conclusions This study is the first to demonstrate that code status affects decision making by nursing staff. It highlights the limitations that code status designations create with regard to patient care. By acknowledging that patients with DNR/DNI orders receive different care, we can create systems in which patients are treated equally, regardless of their code status.

The signal-induced proliferation associated family of proteins comprises four members, SIPA1 and SIPA1L1-1L3. Mutations of the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. We found a direct interaction between Sipa1l3 and Epha4, building a functional platform for proper ocular development. Epha4 deficiency phenocopied loss of Sipa1l3 and rescue experiments demonstrated that Epha4 acts up-stream of Sipa1l3 during eye development. Both, Sipa1l3 and Epha4 are required for early eye specification. The ocular phenotype, upon loss of either Epha4 or Sipa1l3, was partially mediated by rax. We demonstrated that canonical Wnt signaling is inhibited downstream of Epha4/Sipa1l3 during normal eye development. Depletion of either Sipa1l3 or Epha4 resulted in an up-regulation of axin2 expression, a direct Wnt/β-catenin target gene. In line with this, Sipa1l3 or Epha4 depletion could be rescued by blocking Wnt/β-catenin or activating non-canonical Wnt signaling. We therefore conclude that this pathomechanism prevents proper eye development and maturation of lens fiber cells resulting in congenital cataracts.