Monocytes and Macrophages as Viral Targets and Reservoirs

Abstract

Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for dissemination, long-term persistence within tissues and virus replication. Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or membrane fusion. These processes play important roles in the mechanisms contributing to the pathogenesis of these agents and in establishing viral genome persistence and latency. Upon viral infection, monocytes respond with an elevated expression of proinflammatory signalling molecules and antiviral responses, as is shown in the case of the influenza, Chikungunya, human herpes and Zika viruses. Human immunodeficiency virus initiates acute inflammation on site during the early stages of infection but there is a shift of M1 to M2 at the later stages of infection. Cytomegalovirus creates a balance between pro- and anti-inflammatory processes by inducing a specific phenotype within the M1/M2 continuum. Despite facilitating inflammation, infected macrophages generally display abolished apoptosis and restricted cytopathic effect, which sustains the virus production. The majority of viruses discussed in this review employ monocytes/macrophages as a repository but certain viruses use these cells for productive replication. This review focuses on viral adaptations to enter monocytes/macrophages, immune escape, reprogramming of infected cells and the response of the host cells.

Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)

“…There can be substantial crosstalk between the intrinsic and extrinsic pathways, triggered in response to activation of Toll-like receptors (TLRs), which usually result from viral infections [35,[37][38][39]. Monocytes are non-dividing cells with a short half-life that circulate in the blood and make viral replication difficult or almost impossible [40]; as such, apoptosis of peripheral blood monocytes has been suggested to be one of the defense mechanisms against viral infection [41,42]. In the present study, ultrastructural photomicrographs of EEHV viral particles in peripheral blood monocytes of persistent EEHV4-infected calves and positive signals of TUNEL assay in monocytes of the EEHV-HD calves suggest that EEHV infection of monocytes seems to be non productive and result in apoptosis of the EEHV-infected cells.…”

Infection Load and Prevalence of Novel Viruses Identified from the Bank Vole Do Not Associate with Exposure to Environmental Radioactivity

“…Spleen and liver are lined with macrophages that ingest pathogens and activate immune defenses. Several viruses, including arteriviruses [57], infect macrophages to gain access to internal organs and to establish a persistent infection [65]. For example, porcine reproductive and respiratory syndrome virus, which is phylogenetically similar to MgAV1, causes reproductive disorders, pneumonia, and growth reduction in swine through infection of alveolar macrophages and cells of monocyte/macrophage lineage [57].…”

Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages

“…Macrophages are a type of innate immunocyte that play crucial roles in the immune and inflammatory responses to pathogen infections [3]. Despite their strong abilities in pathogen killing and antigen presentation, macrophages can also be hijacked by a range of pathogens as a refuge for propagation and immune escape [4]. JEV is a pathogen that hijacks macrophages for early replication, immune escape, and pathogenesis.…”