Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects

Abstract

Enterovirus 71 (EV71) infection causes hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby presenting a serious risk to public health. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially show that the interleukin enhancer-binding factor 2 (ILF2) reduces EV71 50% tissue culture infective dose (TCID50) and attenuates EV71 plaque-formation unit (PFU), thereby repressing EV71 infection. Microarray data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) -differentiated macrophages and human rhabdomyosarcoma (RD) cells. In addition, EV71 nonstructural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm, and it colocalizes with 2B in the cytoplasm. Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein.

PaO2/FiO2 and IL-6 are risk factors of mortality for intensive care COVID-19 patients

“…However, the pandemic caused by SARS‐CoV‐2 is unprecedented. The mortality rates of SARS and MERS were > 10% and 35%, respectively 1 , 2 , while it is only 3.12–5.43% among the hospitalized COVID-19 patients according to the data from National Health Commission of the People's Republic of China and World Health Organization.…”

Enterovirus A71 2B Inhibits Interferon-Activated JAK/STAT Signaling by Inducing Caspase-3-Dependent Karyopherin-α1 Degradation

“…2B could act directly to impact on the replication of enteroviruses. A recent report showed that EV-A71 2B interacted with transcription factor ILF2 in the cytoplasm to inhibit its negative regulation on virus RNA replication, suggesting that viral 2B could modulate EV-A71 replication in a direct manner (Jin et al, 2020).…”

Immunological and physiopathological approach of COVID-19 in pregnancy

“…The mature virion enters the endosome and interacts with toll-like receptors (TLR) from the immune cells to stimulate downstream inflammatory and clot pathways. Despite sharing almost 70% of the amino acid sequences of SARS-CoV-1, and having the same functional receptor (ACE2), SARS-CoV-2 is more contagious than SARS-CoV-1 and MERS-CoV [ 5 , 15 ]. It has two main genomic polymorphisms; the newest and the most predominant one, L type (∼ 70%) is meant to be more aggressive, and spreads quicker than others [ 14 , 16 , 17 ].…”

“…SARS-CoV-2 is the seventh and the larger type of enveloped simple strained RNA coronavirus species that has been demonstrated to be able to infect humans [ 4 ]. The Severe Acute Respiratory Syndrome coronavirus 1 (SARS-CoV-1) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are two zoonotic coronaviruses that were responsible for epidemic outbreaks with a great local impact in 2002 in China, and in 2012 in Saudi Arabia, respectively [ 5 ]. Their global impact, however, was relatively low.…”

“…A low rate of previously exposed individuals in different communities, and the antigenic diversity among coronaviruses, could explain the explosive COVID-19 outbreak [ 6 ]. Researchers have struggled to understand the diversity in the molecular pathways of the human hosts´ immune system responses to SARS-CoV-2 [ 5 – 7 ].…”