Molecular Signatures of Inflammatory Profile and B-Cell Function in Patients with Severe Fever with Thrombocytopenia Syndrome
Angela Park, Su‐Jin Park, Kyle L. Jung, Se‐Mi Kim, Eun-Ha Kim, Young‐Il Kim, Suan‐Sin Foo, Sung‐Hyun Kim, Seong-Gyu Kim, Kwang-Min Yu, Younho Choi, Younho Choi, Ji Yeun Kim, Yun Hee Baek, Min‐Suk Song, Seung Ryul Kim, Seok-Yong Kim, Hye Won Jeong, Sung‐Han Kim, Jae U. Jung, Young Ki Choi, Young Ki Choi
Abstract
SFTSV is an emerging virus discovered in China in 2009; it has since spread to other countries in East Asia. Although the fatality rates of SFTSV infection range from 5.3% to as high as 27%, the mechanisms underlying clinical manifestations are largely unknown. In this study, we demonstrated that SFTSV infection in fatal cases caused an excessive inflammatory response through high induction of proinflammatory cytokines and chemokines and the aberrant inactivation of adaptive immune responses. Furthermore, single-cell transcriptome sequencing (RNA-seq) analysis of SFTS patient PBMCs revealed that SFTSV targets the B-cell lineage population, especially plasma cells, as the potential viral reservoir in patients for whom the infection is fatal. Thus, SFTSV infection may inhibit high-affinity antibody maturation and secretion of plasma B cells, suppressing neutralizing antibody production and thereby allowing significant virus replication and subsequent fatality.