Hematopoietic stem cells and betaherpesvirus latency

Abstract

The human betaherpesviruses including human cytomegalovirus (HCMV), human herpesvirus (HHV)-6a and HHV-6b, and HHV-7 infect and establish latency in CD34+ hematopoietic stem and progenitor cells (HPCs). The diverse repertoire of HPCs in humans and the complex interactions between these viruses and host HPCs regulate the viral lifecycle, including latency. Precise manipulation of host and viral factors contribute to preferential maintenance of the viral genome, increased host cell survival, and specific manipulation of the cellular environment including suppression of neighboring cells and immune control. The dynamic control of these processes by the virus regulate inter- and intra-host signals critical to the establishment of chronic infection. Regulation occurs through direct viral protein interactions and cellular signaling, miRNA regulation, and viral mimics of cellular receptors and ligands, all leading to control of cell proliferation, survival, and differentiation. Hematopoietic stem cells have unique biological properties and the tandem control of virus and host make this a unique environment for chronic herpesvirus infection in the bone marrow. This review highlights the elegant complexities of the betaherpesvirus latency and HPC virus-host interactions.

Update on human herpesvirus 7 pathogenesis and clinical aspects as a roadmap for future research

“…Upon primary infection, HHV-7 genomes are maintained as episomes in the nucleus of latently infected cells such as resting T cells ( 20 , 37 , 48 ). As described for other betaherpesviruses, HHV-7 may also be able to establish latency in bone marrow-derived hematopoietic progenitor cells ( 70 , 71 ). The latent stage is sporadically interrupted by periods of lytic replication in a subset of latently infected cells, during which infectious progeny is produced.…”

The impact of COVID-19 on microRNA and CD marker expression in AML patients

“…Haematopoiesis is a highly regulated process controlled by complex molecular events that concurrently regulate hematopoietic stem cells’ commitment, differentiation, proliferation, and apoptosis. Substantial evidence now exists to demonstrate that microRNAs modulate haematopoiesis at the level of proliferation and differentiation and act as regulators of hematopoietic cell activity 41 . Differential expression of microRNAs in malignant cells compared to normal cells can be justified by their gene placement in cancer-related genomic regions, epigenetic mechanisms, and alterations in their processing mechanisms 42 , 43 .…”

cGAS-STING-TBK1 Signaling Promotes Valproic Acid-Responsive Human Cytomegalovirus Immediate-Early Transcription during Infection of Incompletely Differentiated Myeloid Cells

“…Human cytomegalovirus (HCMV) is a widespread herpesvirus that causes severe disease in immunocompromised individuals and birth defects in neonates, and it has been associated with cardiovascular diseases and certain tumors [ 1 , 2 ]. HCMV establishes a lifelong infection in its hosts, in part through the establishment of latency in incompletely differentiated cells of the myeloid lineage, such as CD34+ hematopoietic progenitor cells and CD14+ monocytes [ 3 , 4 , 5 ]. Latent reservoirs are not cleared by either the adaptive immune response or existing antiviral therapies [ 6 , 7 ].…”