Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease.
机构:
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Belzile, Jean-Philippe
Stark, Thomas J.
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Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Stem Cell Program, La Jolla, CA USA
Inst Genom Med, La Jolla, CA USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Stark, Thomas J.
Yeo, Gene W.
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机构:
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Stem Cell Program, La Jolla, CA USA
Inst Genom Med, La Jolla, CA USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Yeo, Gene W.
Spector, Deborah H.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
机构:
Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA
NYU, Dept Psychiat, New York, NY 10016 USA
NYU, Dept Cell Biol, New York, NY 10016 USA
NYU, Dept Neurosci, New York, NY 10016 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
Kumar, Asok
Lee, Sooyeon
论文数: 0引用数: 0
h-index: 0
机构:
Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA
NYU, Dept Psychiat, New York, NY 10016 USA
NYU, Dept Cell Biol, New York, NY 10016 USA
NYU, Dept Neurosci, New York, NY 10016 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
机构:
New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
Wegiel, Jerzy
Yu, W. Haung
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h-index: 0
机构:
Columbia Univ, Taub Inst, New York, NY 10032 USA
Columbia Univ, Dept Pathol, New York, NY 10032 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
Yu, W. Haung
Nixon, Ralph A.
论文数: 0引用数: 0
h-index: 0
机构:
Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA
NYU, Dept Psychiat, New York, NY 10016 USA
NYU, Dept Cell Biol, New York, NY 10016 USA
NYU, Dept Neurosci, New York, NY 10016 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
机构:
Univ Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Buckingham, Erin M.
Carpenter, John E.
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Univ Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Carpenter, John E.
Jackson, Wallen
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Univ Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Jackson, Wallen
Zerboni, Leigh
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机构:
Stanford Univ, Med Ctr, Sch Med, Dept Pediat, Stanford, CA 94305 USA
Stanford Univ, Med Ctr, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Zerboni, Leigh
Arvin, Ann M.
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h-index: 0
机构:
Stanford Univ, Med Ctr, Sch Med, Dept Pediat, Stanford, CA 94305 USA
Stanford Univ, Med Ctr, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
机构:
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Belzile, Jean-Philippe
Stark, Thomas J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Stem Cell Program, La Jolla, CA USA
Inst Genom Med, La Jolla, CA USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Stark, Thomas J.
Yeo, Gene W.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Stem Cell Program, La Jolla, CA USA
Inst Genom Med, La Jolla, CA USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Yeo, Gene W.
Spector, Deborah H.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
机构:
Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA
NYU, Dept Psychiat, New York, NY 10016 USA
NYU, Dept Cell Biol, New York, NY 10016 USA
NYU, Dept Neurosci, New York, NY 10016 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
Kumar, Asok
Lee, Sooyeon
论文数: 0引用数: 0
h-index: 0
机构:
Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA
NYU, Dept Psychiat, New York, NY 10016 USA
NYU, Dept Cell Biol, New York, NY 10016 USA
NYU, Dept Neurosci, New York, NY 10016 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
机构:
New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
Wegiel, Jerzy
Yu, W. Haung
论文数: 0引用数: 0
h-index: 0
机构:
Columbia Univ, Taub Inst, New York, NY 10032 USA
Columbia Univ, Dept Pathol, New York, NY 10032 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
Yu, W. Haung
Nixon, Ralph A.
论文数: 0引用数: 0
h-index: 0
机构:
Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA
NYU, Dept Psychiat, New York, NY 10016 USA
NYU, Dept Cell Biol, New York, NY 10016 USA
NYU, Dept Neurosci, New York, NY 10016 USAUniv Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland
机构:
Univ Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Buckingham, Erin M.
Carpenter, John E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Carpenter, John E.
Jackson, Wallen
论文数: 0引用数: 0
h-index: 0
机构:
Univ Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Jackson, Wallen
Zerboni, Leigh
论文数: 0引用数: 0
h-index: 0
机构:
Stanford Univ, Med Ctr, Sch Med, Dept Pediat, Stanford, CA 94305 USA
Stanford Univ, Med Ctr, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA
Zerboni, Leigh
Arvin, Ann M.
论文数: 0引用数: 0
h-index: 0
机构:
Stanford Univ, Med Ctr, Sch Med, Dept Pediat, Stanford, CA 94305 USA
Stanford Univ, Med Ctr, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USAUniv Iowa, Childrens Hosp, Dept Pediat, Virol Lab, Iowa City, IA 52242 USA