Characterization of Infections of Human Leukocytes by Non-Polio Enteroviruses

Abstract

To elucidate the detailed susceptibilities of leukocytes to clinically important non-polio enteroviruses (EVs), primary monocytes and various human leukocyte cell lines were infected with coxsackievirus A24 (CVA24), coxsackievirus B3 (CVB3), and enterovirus 70 (EV70). The permissiveness was then assessed by determining virus replication and resultant cytopathic effects. Different EVs varied markedly in their ability to infect leukocyte cell lines. CVB3 replicated effectively in leukocytes of B-cell, T-cell, and monocyte origin, CVA24 in leukocytes of B-cell and monocyte origin, and EV70 in leukocytes of monocyte origin. Primary monocytes, as well as monocyte-derived U-937 cells, were permissive to all three EVs. We observed a positive correlation between cytotoxicity and active virus replication, except in CVB3-infected monocytes. U-937 cells efficiently generated CVB3 progeny virus without severe cellular damage, including cell death. Moreover, infectivity on leukocytes was not absolutely associated with the availability of viral receptors. These findings suggest that the susceptibility of human leukocytes to non-polio EVs may be responsible for virus transport during the viremic phase, particularly to secondary target organs, and that active replication of CVB3 in all human leukocyte lineages leads to greater dissemination, in agreement with the ability of CVB to cause systemic diseases.

Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study

“…Our source of RNA (i.e. packed blood cells) may bear a certain 'memory' of past viral infections because peripheral white blood cells are permissive to enterovirus infection [16] and may be a better source of enterovirus RNA than plasma or serum [17,18]. Thus, we speculate that the enterovirus positivity we observed may reflect infection occurring over longer periods of time, leaving the direction of the causality unresolved.…”

Epidemiology and Immune Pathogenesis of Viral Sepsis

“…Some viral infections can directly result in immune suppression. Some strains of enterovirus are known to infect leucocytes ( 212 ). In particular some strains, such as coxsackievirus B3 and enterovirus 70, that have been implicated as causes of sepsis have shown this capacity ( 212 ).…”

“…Some strains of enterovirus are known to infect leucocytes ( 212 ). In particular some strains, such as coxsackievirus B3 and enterovirus 70, that have been implicated as causes of sepsis have shown this capacity ( 212 ). Infection of leucocytes in severe viral infections has been shown to result in an immunosuppressed state, as the death of infected leucocytes can result in a diminished ability to prime CD4 and CD8 cells and a reduced ability to control pathogens by phagocytosis.…”

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

“…Infection of mice by CVB3 showed that B cells were susceptible to viral infection and also helped disseminate the virus during early infection to the brain and other tissues throughout the body (Mena et al, 1999). CVB3 was shown to replicate in several in vitro cell lines including Raji (B cell), Jurkat (T cell) and U-937 (monocyte) (Hwang et al, 2012) implicating these cell types to possibly serve as viral shuttles into the CNS. Poliovirus was shown to infect monocytes (Freistadt et al, 1993;Freistadt and Eberle, 1996), EV71 was able to replicate in CD14+ cells , dendritic cells (Lin et al, 2009) and PBMCs (Wongsa et al, 2019) while echoviruses (1, 7, 8, and 9) replicated in mature dendritic cells isolated from PBMCs but not monocytes (Kramer et al, 2007).…”