No abstract

Six years have passed since the outbreak of severe acute respiratory syndrome (SARS). Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time in recovered SARS patients. It is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another SARS outbreak. Recovered SARS patients were followed up to 6 y to estimate the longevity of specific Ab. The specific memory B cell and T cell responses to SARS-CoV Ags were measured by means of ELISPOT assay. Factors in relation to humoral and cellular immunity were investigated. Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients. Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls. Patients with more severe clinical manifestations seemed to present a higher level of Ag-specific memory T cell response. SARS-specific IgG Ab may eventually vanish and peripheral memory B cell responses are undetectable in recovered SARS patients. In contrast, specific T cell anamnestic responses can be maintained for at least 6 y. These findings have applications in preparation for the possible reemergence of SARS.

No abstract

The recent Zika virus (ZIKV) epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal (i.p.) injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial glia cells (RGs) of dorsal ventricular zone of the fetuses, the primary neural progenitors responsible for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports the conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies.

In a cohort study of 56 convalescent patients with severe acute respiratory syndrome (SARS), titers of immunoglobulin G (IgG) antibodies and neutralizing antibodies (NAbs) against SARS-associated coronavirus were assessed at regular intervals (at 1, 4, 7, 10, 16, and 24 months after the onset of disease) by use of enzyme-linked immunosorbent assay and neutralization assay. IgG antibody and NAb titers were highly correlated, peaking at month 4 after the onset of disease and decreasing thereafter. IgG antibodies remained detectable in all patients until month 16, and they became undetectable in 11.8% of patients at month 24. The finding that NAbs remained detectable throughout follow-up is reassuring in terms of protection provided against reinfection; however, NAb titers decreased markedly after month 16.

No abstract

For antiviral signaling mediated by retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), the recruitment of cytosolic RLRs and downstream molecules (such as TBK1 and IKKε) to mitochondrial platform is a central event that facilitates the establishment of host antiviral state. Here, we present an example of viral targeting for immune evasion through spatial isolation of TBK1/IKKε from mitochondrial antiviral platform, which was employed by severe fever with thrombocytopenia syndrome virus (SFTSV), a deadly bunyavirus emerging recently. We showed that SFTSV nonstructural protein NSs functions as the interferon (IFN) antagonist, mainly via suppressing TBK1/IKKε-IRF3 signaling. NSs mediates the formation of cytoplasmic inclusion bodies (IBs), and the blockage of IB formation impairs IFN-inhibiting activity of NSs. We next demonstrate that IBs are utilized to compartmentalize TBK1/IKKε. The compartmentalization results in spatial isolation of the kinases from mitochondria, and deprived TBK1/IKKε may participate in antiviral complex assembly, leading to the blockage of IFN induction. This study proposes a new role of viral IBs as virus-built 'jail' for imprisoning cellular factors and presents a novel and likely common mechanism of viral immune evasion through spatial isolation of critical signaling molecules from the mitochondrial antiviral platform.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high case fatality rate of up to 30% (1-3). The causative agent is a novel phlebovirus of the Bunyaviridae family, namely, SFTS virus (SFTSV), which was identified first in China and subsequently was found in South Korea (4, 5) and Japan (6). Recently, another phlebovirus genetically closely related to SFTSV was isolated in the United States (7). Emerging bunyavirus infection has become a substantial threat to public health; however, the pathogenesis is largely unknown, and there are no vaccines or specific antivirals available. The SFTSV genome consists of three single-stranded RNA segments. The large (L) and medium (M) segments are of negative polarity and encode the RNA-dependent RNA polymerase and the glycoprotein precursor, respectively, while the small segment (S) encodes the nucleoprotein (NP) and the nonstructural protein (NSs) by an ambisense strategy. Although little is known on SFTSV-host interactions, studies have suggested that the NSs protein is implicated in viral suppression of host antiviral innate immunity; thus, it likely is contributing to viral pathogenesis (8-10).Antiviral innate immune response is initiated through the recognition of virus infection by cellular pattern recognition receptors (PRRs), such as transmembrane toll-like receptor 3 (TLR3) and cytosolic RIG-I-like receptors RIG-I and MDA5 (11). Upon recognition, PRRs trigger the signaling cascades that lead to the induction of type I interferons (IFNs) through the activation of transcription factors, such as interferon regulatory factors (IRFs) 3 and 7 and NF-B. The newly synthesized and secreted type I IFNs bind to their receptors on the cell surface and result in the phosphorylation of signal transducer and activator of transcription 2 (STAT2) and 1 (STAT1), transcription factors that are the key components of type I IFN signaling pathway, by Janus kinases (JAKs). The phosphorylated STATs then heterodimerize and as-