Human Cytomegalovirus Latency and Reactivation in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Lauren Stern,Barbara Withers,Barry Slobedman,Allison Abendroth,Emily Blyth,David Gottlieb,Selmir Avdic

doi:10.3389/fmicb.2019.01186

Abstract

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.

Highlights

Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by a majority of the global population (Cannon et al, 2010; Zuhair et al, 2019)
Intermittent subclinical viral reactivation events are thought to be controlled by effective immune surveillance and may drive the high frequencies of HCMV-specific T-cells found in the peripheral blood of healthy seropositive individuals (Sester et al, 2002; Sylwester et al, 2005)
Reactivation from latency is responsible for significant morbidity and mortality in immunocompromised and immunosuppressed populations, Cytomegalovirus Reactivation in HSCT Recipients including solid-organ transplant and allogeneic hematopoietic stem cell transplant (HSCT) recipients, HIV/AIDS patients and the developing fetus

Summary

Introduction

Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by a majority of the global population (Cannon et al, 2010; Zuhair et al, 2019). Quantitative thresholds of CD8+ and CD4+ HCMV-specific T-cells associated with protection from, or control of, reactivation or disease post-HSCT have been defined using HLA tetramers or ex vivo viral stimulation assays (Aubert et al, 2001; Cwynarski et al, 2001; Gratama et al, 2001, 2010; Lilleri et al, 2008; MoinsTeisserenc et al, 2008; Borchers et al, 2011, 2012; Tormo et al, 2011; Lilleri et al, 2012; Liu et al, 2016).

Results

Conclusion