Case report: painful exanthems caused by enterovirus D68 in an adolescent

Chang, Tu‐Hsuan; Yang, Ting‐Hua; Hsu, Wei-Yun; Huang, Li‐Min; Chang, Luan‐Yin; Lu, Chi-Jen

doi:10.1097/md.0000000000016493

Cited by 4 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since poliovirus viremia is essential for virus spread to the CNS and the subsequent development of poliomyelitis ( 41 ), it can be speculated that EV-D68 viremia is one of the mechanisms that is essential for virus entry into the CNS and the subsequent development of AFM ( 3 , 14 ). In addition, a viremia could lead to virus spread to other organ system contributing to non-neurological complications associated with EV-D68 infection, including acute gastroenteritis, myocarditis, and skin rash ( 42 – 44 ). Prevention of spread to, or productive infection of lymphoid tissues may prevent systemic dissemination, as observed in poliovirus infection, in which vaccination prevents viral spread to other organs ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection

Laksono,

Sooksawasdi Na Ayudhya,

Aguilar-Bretones

et al. 2024

mSphere

View full text Add to dashboard Cite

Enterovirus D68 (EV-D68) is predominantly associated with mild respiratory infections, but can also cause severe respiratory disease and extra-respiratory complications, including acute flaccid myelitis. Systemic dissemination of EV-D68 is crucial for the development of extra-respiratory diseases, but it is currently unclear how EV-D68 spreads systemically (viremia). We hypothesize that immune cells contribute to the systemic dissemination of EV-D68, as this is a mechanism commonly used by other enteroviruses. Therefore, we investigated the susceptibility and permissiveness of human primary immune cells for different EV-D68 isolates. In human peripheral blood mononuclear cells inoculated with EV-D68, only B cells were susceptible but virus replication was limited. However, in B cell-rich cultures, such as Epstein–Barr virus-transformed B-lymphoblastoid cell line (BLCL) and primary lentivirus-transduced B cells, which better represent lymphoid B cells, were productively infected. Subsequently, we showed that dendritic cells (DCs), particularly immature DCs, are susceptible and permissive for EV-D68 infection and that they can spread EV-D68 to autologous BLCL. Altogether, our findings suggest that immune cells, especially B cells and DCs, could play an important role in the pathogenesis of EV-D68 infection. Infection of these cells may contribute to systemic dissemination of EV-D68, which is an essential step toward the development of extra-respiratory complications. IMPORTANCE Enterovirus D68 (EV-D68) is an emerging respiratory virus that has caused outbreaks worldwide since 2014. EV-D68 infects primarily respiratory epithelial cells resulting in mild respiratory diseases. However, EV-D68 infection is also associated with extra-respiratory complications, including polio-like paralysis. It is unclear how EV-D68 spreads systemically and infects other organs. We hypothesized that immune cells could play a role in the extra-respiratory spread of EV-D68. We showed that EV-D68 can infect and replicate in specific immune cells, that is, B cells and dendritic cells (DCs), and that virus could be transferred from DCs to B cells. Our data reveal a potential role of immune cells in the pathogenesis of EV-D68 infection. Intervention strategies that prevent EV-D68 infection of immune cells will therefore potentially prevent systemic spread of virus and thereby severe extra-respiratory complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection

Laksono,

Sooksawasdi Na Ayudhya,

Aguilar-Bretones

et al. 2024

mSphere

View full text Add to dashboard Cite

show abstract

“…Since poliovirus viremia is essential for virus spread to the CNS and the subsequent development of CNS diseases (37), it can be speculated that EV-D68 viremia is essential for virus entry into the CNS and subsequent neurological complications, such as AFM (4,13). In addition, a viremia could lead to virus spread to other organ system contributing to non-neurological complications associated with EV-D68 infection, including acute gastroenteritis, myocarditis and skin rash (38)(39)(40). Prevention of spread or productive infection in the lymphoid tissues may prevent systemic dissemination, as observed in poliovirus infection, in which vaccination prevents viral spread to other organs (41).…”

Section: Discussionmentioning

confidence: 99%

The potential role of human immune cells in the systemic dissemination of enterovirus-D68

Laksono

Ayudhya

Aguilar-Bretones

et al. 2022

Preprint

View full text Add to dashboard Cite

Enterovirus-D68 (EV-D68) often causes mild respiratory infections, but can also cause severe respiratory infections and extra-respiratory complications, including acute flaccid myelitis (AFM). Systemic dissemination of EV-D68 is crucial for the development of extra-respiratory diseases, but it is currently unclear how EV-D68 viremia occurs. We hypothesize that immune cells contribute to the systemic dissemination of EV-D68, as this is a mechanism commonly used by other enteroviruses. Therefore, we investigated the susceptibility and permissiveness of human primary immune cells for different EV-D68 isolates. In human peripheral blood mononuclear cells (PBMC) inoculated with EV-D68, only B cells were susceptible but virus replication was limited. However, B cell-rich cultures, such as Epstein-Barr virus-transformed B-lymphoblastoid cell line (BLCL) and primary lentivirus-transduced B cells, were productively infected. In BLCL, neuraminidase treatment to remove α2,6- and α2,3-linked sialic acids resulted in a significant decrease of EV-D68 infected cells, suggesting that sialic acids are the functional receptor on B cells. Subsequently, we showed that dendritic cells (DCs), particularly immature DCs, are susceptible and permissive for EV-D68 infection and that they can spread EV-D68 to autologous BLCL. Altogether, our findings suggest that immune cells, especially B cells and DCs, play an important role in the development the systemic dissemination of EV-D68 during an infection, which is an essential step towards the development of extra-respiratory complications.

show abstract

“…Some patients with EV-D68 infection developed cardiac symptoms, such as myocarditis, pericarditis and acute cardiac failure [72]. Several clinical cases have reported the appearance of skin rash in EV-D68 patients [73][74][75]. Whether the virus infects the cells of the heart, which leads to cardiac symptoms, or the dermis and epidermis, which leads to skin rash, remains to be determined.…”

Section: Systemic Dissemination Of Ev-d68mentioning

confidence: 99%