Long-term follow-up of post-cardiac surgery Mycobacterium chimaera infections: A 5-center case series.

OBJECTIVES: In multiple countries, endovascular/disseminated Mycobacterium chimaera infections have occurred in post-cardiac surgery patients in association with contaminated, widely-distributed cardiac bypass heater-cooler devices. To contribute to long-term characterization of this recently recognized infection, we describe the clinical course of 28 patients with 3-7 years of follow-up for survivors. METHODS: Identified at five hospitals in the United States 2010-2016, post-cardiac surgery patients in the cohort had growth of Mycobacterium avium complex (MAC)/M. chimaera from a sterile site or surgical wound, or a clinically compatible febrile illness with granulomatous inflammation on biopsy. Case follow-up was conducted in May 2019. RESULTS: Of 28 patients, infection appeared to be localized to the sternum in four patients. Among 18 with endovascular/disseminated infection who received combination anti-mycobacterial treatment and had sufficient follow-up, 39% appeared to have controlled infection (>12 months), 56% died, and one patient is alive with relapsed bacteremia. While the number of patients is small and interpretation is limited, four (67%) of six patients who had cardiac prosthesis removal/replacement appeared to have controlled infection compared to three (25%) of 12 with retained cardiac prosthesis (p >0.14; Fisher's exact test). CONCLUSIONS: Given poor response to treatment and potential for delayed relapses, post-cardiac surgery M. chimaera infection warrants aggressive treatment and long-term monitoring.

Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction and glucocorticoid-mediated signaling.

Human immunodeficiency virus, type 1 (HIV-1) vpr is a highly conserved gene among lentiviruses. The diverse functions of Vpr support interactions of this HIV accessory protein with host cell partners of important pathways. hVIP/mov34 (human Vpr Interacting Protein) is one of these identified Vpr ligands. hVIP is a 34-kDa member of the eIF3 family that is vital for early embryonic development in transgenic mice and important in cell cycle regulation. Its interaction with Vpr, however, is not yet clearly defined. Therefore, we constructed a panel of deletion mutants of this cytoplasmic cellular ligand to map the protein domain that mediates its interaction with Vpr. We observed that the carboxyl-terminal region of hVIP is critical for its interaction with Vpr. In the absence of Vpr or HIV infection, full-length hVIP is expressed in the cytoplasm. The cytoplasmic localization pattern of full-length hVIP protein, however, is shifted to a clear nuclear localization pattern in cells expressing both hVIP and Vpr. In contrast, Vpr did not alter the localization pattern of hVIP mutants, which have their carboxyl-terminal domain deleted. The movement of hVIP supported prior work that suggested that Vpr triggers activation of the GR receptor complex. In fact, we also observed that dexamethasone moves hVIP into the nucleus and that glucocorticoid antagonists inhibit this effect. Interestingly, the expression of an hVIP carboxyl-terminal mutant, which is not responsive to Vpr, is also not responsive to dexamethasone. These data illustrate that the carboxyl-terminal domain of hVIP is critical for mediating hVIP-Vpr interaction as well as for its glucocorticoid response. These results support the view that hVIP is a member of the complex array of nucleocytoplasmic shuttling proteins that are regulated by HIV infection and glucocorticoids.