Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells.

UNLABELLED: Measles is a highly contagious, acute viral illness. Immune cells within the airways are likely first targets of infection, and these cells traffic measles virus (MeV) to lymph nodes for amplification and subsequent systemic dissemination. Infected immune cells are thought to return MeV to the airways; however, the mechanisms responsible for virus transfer to pulmonary epithelial cells are poorly understood. To investigate this process, we collected blood from human donors and generated primary myeloid cells, specifically, monocyte-derived macrophages (MDMs) and dendritic cells (DCs). MDMs and DCs were infected with MeV and then applied to primary cultures of well-differentiated airway epithelial cells from human donors (HAE). Consistent with previous results obtained with free virus, infected MDMs or DCs were incapable of transferring MeV to HAE when applied to the apical surface. Likewise, infected MDMs or DCs applied to the basolateral surface of HAE grown on small-pore (0.4-µm) support membranes did not transfer virus. In contrast, infected MDMs and DCs applied to the basolateral surface of HAE grown on large-pore (3.0-µm) membranes successfully transferred MeV. Confocal microscopy demonstrated that MDMs and DCs are capable of penetrating large-pore membranes but not small-pore membranes. Further, by using a nectin-4 blocking antibody or recombinant MeV unable to enter cells through nectin-4, we demonstrated formally that transfer from immune cells to HAE occurs in a nectin-4-dependent manner. Thus, both infected MDMs and DCs rely on cell-to-cell contacts and nectin-4 to efficiently deliver MeV to the basolateral surface of HAE. IMPORTANCE: Measles virus spreads rapidly and efficiently in human airway epithelial cells. This rapid spread is based on cell-to-cell contact rather than on particle release and reentry. Here we posit that MeV transfer from infected immune cells to epithelial cells also occurs by cell-to-cell contact rather than through cell-free particles. In addition, we sought to determine which immune cells transfer MeV infectivity to the human airway epithelium. Our studies are based on two types of human primary cells: (i) myeloid cells generated from donated blood and (ii) well-differentiated airway epithelial cells derived from donor lungs. We show that different types of myeloid cells, i.e., monocyte-derived macrophages and dendritic cells, transfer infection to airway epithelial cells. Furthermore, cell-to-cell contact is an important component of successful MeV transfer. Our studies elucidate a mechanism by which the most contagious human respiratory virus is delivered to the airway epithelium.

Anxiety-Related Issues in Cancer Survivorship.

PURPOSE: The purpose of this qualitative study was to examine patient opinions about anxiety in cancer survivorship, particularly the role of the primary care provider in management of anxiety related to the trajectory of long-term cancer survivorship. METHODS: Respondents to a mass email (N=22,000) were invited to participate in 1 of 3 institutional review board-approved focus group meetings. Inclusion criteria were being an adult patient older than 25 years of age, having any type of cancer diagnosis, and being at least 18 months from treatment. The following specific issues were discussed: role of the primary care provider during and after therapy; the transition to primary care after therapy was finished; and advice the survivors would give to providers and cancer survivors. Focus group meetings were audio-recorded and later transcribed and reviewed by members of the research team using constant comparison methods. RESULTS: Three 2-hour focus groups were conducted to interview 22 cancer survivors. We found 5 main themes related to anxiety in cancer survivorship: memory of anxiety; anxiety related to possible cancer recurrence; role of close relationship with the health care provider in anxiety management; frequency of communication in reduction of anxiety symptoms; and effect of anxiety on future health decisions posttreatment. CONCLUSIONS: Survivors described anxiety persisting throughout cancer diagnosis and treatment and well into survivorship. They reported receiving care from primary care providers as well as oncologists. Anxiety was discussed by most participants as a significant part of their experience with cancer.