Human cytomegalovirus (HCMV) reactivation is a major infectious cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). HCMV is a ubiquitous beta-herpesvirus which asymptomatically infects immunocompetent individuals but establishes lifelong latency, with the potential to reactivate to a life-threatening productive infection when the host immune system is suppressed or compromised. Opportunistic HCMV reactivation is the most common viral complication following engraftment after HSCT and is associated with a marked increase in non-relapse mortality, which appears to be linked to complex effects on post-transplant immune recovery. This minireview explores the cellular sites of HCMV latency and reactivation in HSCT recipients and provides an overview of the risk factors for HCMV reactivation post-HSCT. The impact of HCMV in shaping post-transplant immune reconstitution and its relationship with patient outcomes such as relapse and graft-versus-host disease will be discussed. Finally, we survey current and emerging strategies to prevent and control HCMV reactivation in HSCT recipients, with recent developments including adoptive T cell therapies to accelerate HCMV-specific T cell reconstitution and new anti-HCMV drug therapy for HCMV reactivation after HSCT.

Mass cytometry, or Cytometry by Time-Of-Flight, is a powerful new platform for high-dimensional single-cell analysis of the immune system. It enables the simultaneous measurement of over 40 markers on individual cells through the use of monoclonal antibodies conjugated to rare-earth heavy-metal isotopes. In contrast to the fluorochromes used in conventional flow cytometry, metal isotopes display minimal signal overlap when resolved by single-cell mass spectrometry. This review focuses on the potential of mass cytometry as a novel technology for studying immune reconstitution in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Reconstitution of a healthy donor-derived immune system after HSCT involves the coordinated regeneration of innate and adaptive immune cell subsets in the recipient. Mass cytometry presents an opportunity to investigate immune reconstitution post-HSCT from a systems-level perspective, by allowing the phenotypic and functional features of multiple cell populations to be assessed simultaneously. This review explores the current knowledge of immune reconstitution in HSCT recipients and highlights recent mass cytometry studies contributing to the field.

Human cytomegalovirus (HCMV) continues to cause serious and often life-threatening disease in those with impaired or underdeveloped immune systems. This virus is able to infect and replicate in a wide range of human cell types, which enables the virus to spread to other individuals in a number of settings. Current antiviral drugs are associated with a significant toxicity profile, and there is no vaccine; these factors highlight a need to identify additional targets for the development of anti-HCMV therapies. We demonstrate for the first time that secretion of a member of the galectin family of proteins, galectin-9 (Gal-9), is upregulated during natural HCMV-reactivated infection and that this soluble cellular protein possesses a potent capacity to block HCMV infection by inhibiting virus entry into the host cell. Our findings support the possibility of harnessing the antiviral properties of Gal-9 to prevent HCMV infection and disease.

Both typical and atypical antipsychotic psychotropics have been reported to cause ischemic priapism presumptively secondary to alpha1-adrenergic blockade. This condition is a urologic emergency for if not evaluated and treated appropriately, long-term sequelae include erectile dysfunction and impotence. This paper addresses the first reported case of priapism requiring surgical intervention presumed to be secondary to ziprasidone. Increased clinician and patient education regarding priapism is required in order to minimize this adverse event and to maximize immediate treatment.

Human cytomegalovirus reactivation is a major opportunistic infection after allogeneic haematopoietic stem cell transplantation and has a complex relationship with post-transplant immune reconstitution. Here, we use mass cytometry to define patterns of innate and adaptive immune cell reconstitution at key phases of human cytomegalovirus reactivation in the first 100 days post haematopoietic stem cell transplantation. Human cytomegalovirus reactivation is associated with the development of activated, memory T-cell profiles, with faster effector-memory CD4⁺ T-cell recovery in patients with low-level versus high-level human cytomegalovirus DNAemia. Mucosal-associated invariant T cell levels at the initial detection of human cytomegalovirus DNAemia are significantly lower in patients who subsequently develop high-level versus low-level human cytomegalovirus reactivation. Our data describe distinct immune signatures that emerged with human cytomegalovirus reactivation after haematopoietic stem cell transplantation, and highlight Mucosal-associated invariant T cell levels at the first detection of reactivation as a marker that may be useful to anticipate the magnitude of human cytomegalovirus DNAemia.

Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that infects mucosal sites and adopts an arsenal of strategies to manipulate host immunity. Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes that recognize bacterial and fungal-derived vitamin B-related metabolites presented by major histocompatibility complex class I-related protein 1 (MR1). MAIT cells can also be activated in an MR1-independent manner via cytokine stimulation, predominantly by IL-12 and IL-18. MAIT cell alterations have been identified as being associated with a number of viral infections, but direct interactions between viruses and MAIT cells are poorly understood. It is unknown whether HSV-1 can infect MAIT cells and modulate their functions. Here, we show that HSV-1 can infect primary human MAIT cells, including CD4 ^± /CD8 ^± and CD56 ^± MAIT cell subpopulations. Furthermore, HSV-1 infection profoundly inhibits the functional capacity of MAIT cells to respond to T cell receptor (TCR)-dependent stimulation by the MAIT cell activating ligand 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and to cytokine stimulation by IL-12/IL-18. HSV-1-infected MAIT cells display reduced cytotoxic potential, diminished synthesis of effector cytokines, and decreased expression of key cytokine receptors including IL-18R. In addition, MAIT cells exposed to HSV-1-infected fibroblasts but which remained uninfected (viral GFP-negative) also exhibit a suppressed effector response to TCR-dependent stimulation. The functional suppression of HSV-1-exposed MAIT cells was not mediated by a soluble factor within the supernatant, suggesting direct contact of MAIT cells with HSV-1-infected fibroblasts is required. Overall, this study reveals that HSV-1 can infect MAIT cells and substantially impair MAIT cell effector functions. IMPORTANCE: Mucosal-associated invariant T cells (MAIT cells) are “unconventional” immune cells that are becoming increasingly appreciated to play important roles in a variety of viral infections. Herpes simplex virus (HSV) causes significant human disease and is a master manipulator of multiple immune functions, but how this virus may control MAIT cells is poorly understood. We discovered that HSV can infect human MAIT cells and impair their functional capacity and also show that MAIT cells exposed to HSV, but which do not show evidence of infection, are similarly impaired. This study therefore identifies an additional immunomodulatory function of HSV.