TY - JOUR
T1 - Bortezomib induces HSV-1 lethality in mice with neutrophil deficiency
AU - Yao, Hui Wen
AU - Wang, Li Chiu
AU - Tsai, Hsien Yang
AU - Fang, Yi Hsuan
AU - Zheng, Chunfu
AU - Chen, Shun Hua
AU - Hsu, Sheng Min
N1 - Funding Information:
We thank Donald Coen, Robert Lausch, Wei‐Li Hsu, and Chia‐Chi Ku for providing viruses used in this study and/or helpful suggestions. This work was supported by grants from the Ministry of Science and Technology in Taiwan to S.‐M.H. (MOST 103‐2314‐B‐006‐067) and to S.‐H.C. (MOST 108‐2320‐B‐006‐035‐MY3).
Publisher Copyright:
©2019 Society for Leukocyte Biology
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Bortezomib suppressing NF-κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV-1 can reactivate to induce mortality. The important issues regarding how bortezomib diminishes neutrophils, whether bortezomib can induce HSV-1 reactivation, and how bortezomib exacerbates HSV-1 infection, need investigation. Using the murine model, we found that bortezomib induced HSV-1 reactivation. Bortezomib diminished neutrophil numbers in organs of uninfected and HSV-1-infected mice and turned a nonlethal infection to lethal with elevated tissue viral loads. In vitro results showed that bortezomib and HSV-1 collaborated to enhance the death and apoptosis of mouse neutrophils. The leukocyte deficiency induced by chemotherapies is generally believed to be the cause for aggravating virus infections. Here we show the potential of pathogen to exacerbate chemotherapy-induced leukocyte deficiency.
AB - Bortezomib suppressing NF-κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV-1 can reactivate to induce mortality. The important issues regarding how bortezomib diminishes neutrophils, whether bortezomib can induce HSV-1 reactivation, and how bortezomib exacerbates HSV-1 infection, need investigation. Using the murine model, we found that bortezomib induced HSV-1 reactivation. Bortezomib diminished neutrophil numbers in organs of uninfected and HSV-1-infected mice and turned a nonlethal infection to lethal with elevated tissue viral loads. In vitro results showed that bortezomib and HSV-1 collaborated to enhance the death and apoptosis of mouse neutrophils. The leukocyte deficiency induced by chemotherapies is generally believed to be the cause for aggravating virus infections. Here we show the potential of pathogen to exacerbate chemotherapy-induced leukocyte deficiency.
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U2 - 10.1002/JLB.4AB1019-495R
DO - 10.1002/JLB.4AB1019-495R
M3 - Article
C2 - 31729784
AN - SCOPUS:85075385177
VL - 107
SP - 105
EP - 112
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 1
ER -