Development of fatigue measurement method using herpes virus which can distinguish between mental fatigue and physical fatigue

• Project/Area Number: 15K08216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Kondo Kazuhiro 東京慈恵会医科大学, 医学部, 教授 (70234929)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 身体疲労 / 精神疲労 / 生理的疲労 / 病的疲労 / 運動負荷 / HHV-6 / HHV-7 / バイオマーカー / 睡眠不足 / 肝臓 / 炎症性サイトカイン / mRNA / 血液検査

Outline of Final Research Achievements

People recover from physiological fatigue with rest. Pathological mental fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with training and work and rapidly decreased with rest. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome, chronic fatigue syndrome and major depressive disorder, which are thought to cause pathological mental fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological mental fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases.

Research Products

• [Journal Article] Increased interleukin-1β and basic fibroblast growth factor levels in the cerebrospinal fluid during human herpesvirus-6B (HHV-6B) encephalitis (2017)
  • Author(s): Tamai Masato、Kobayashi Nobuyuki、Shimada Kazuya、Oka Naomi、Takahashi Mayumi、Tanuma Akiko、Tanemoto Tomohiro、Namba Hiroyuki、Saito Yoshihiro、Wada Yasuyuki、Okamoto Aikou、Ida Hiroyuki、Kondo Kazuhiro
  • Journal Title: Biochemical and biophysical research communications Volume: 486 Issue: 3 Pages: 706-711
  • DOI: 10.1016/j.bbrc.2017.03.102
  • Peer Reviewed / Open Access
• [Journal Article] Caregiver burden and fatigue in caregivers of people with dementia: Measuring human herpesvirus (HHV)-6 and & -7 DNA levels in saliva, (2016)
  • Author(s): Tohmi Osaki, Takako Morikawa, Hiroyuki Kajita, Nobuyuki Kobayashi, Kazuhiro Kondo, Kiyoshi Maeda.
  • Journal Title: Archives of Gerontology and Geriatrics Volume: 66 Pages: 42-48
  • DOI: 10.1016/j.archger.2016.04.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer's disease and amnesic mild cognitive impairment patients. (2016)
  • Author(s): Shinagawa S, Kobayashi N, Nagata T, Kusaka A, Yamada H, Kondo K, Nakayama K.
  • Journal Title: Neurosci Lett Volume: 629 Pages: 33-37
  • DOI: 10.1016/j.neulet.2016.06.055
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue. (2016)
  • Author(s): Aoki, R., Kobayashi, N., Suzuki, G., Kuratsune, H., Shimada, K., Oka, N., Takahashi, M., Yamadera, W., Iwashita, M., Tokuno, S., Nibuya, M., Tanichi, M., Mukai, Y., Mitani, K., Kondo, K., Ito, H., Nakayama, K.
  • Journal Title: Biochem. Biophy. Res. Commun. Volume: 478 Issue: 1 Pages: 424-430
  • DOI: 10.1016/j.bbrc.2016.07.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Usefulness of DNA Methylation Levels in COASY and SPINT1 Gene Promoter Regions as Biomarkers inDiagnosis of Alzheimer's Disease and Amnestic Mild Cognitive Impairment. (2016)
  • Author(s): Kobayashi N, Shinagawa S, Nagata T, Shimada K, Shibata N, Ohnuma T, Kasanuki K, Arai H, Yamada H, Nakayama K, Kondo K.
  • Journal Title: PloS one Volume: 11 Issue: 12 Pages: e0168816-e0168816
  • DOI: 10.1371/journal.pone.0168816
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of Biomarkers Based on DNA Methylation in the NCAPH2/LMF2 Promoter Region for Diagnosis of Alzheimer’s Disease and Amnesic Mild Cognitive Impairment． (2016)
  • Author(s): Nobuyuki Kobayashi, Shunichiro Shinagawa, Tomoyuki Nagata, Kazuya Shimada, Nobuto Shibata, Tohru Ohnuma, Koji Kasanuki, Heii Arai, Hisashi Yamada, Kazuhiko Nakayama, Kazuhiro Kondo.
  • Journal Title: PLoS ONE Volume: 11(1) Issue: 1 Pages: e0146449-e0146449
  • DOI: 10.1371/journal.pone.0146449
  • Peer Reviewed / Open Access
• [Journal Article] Effects of nutritional supplementation on fatigue, and autonomic and immune dysfunction in patients with end-stage renal disease: a randomized, double-blind, placebo-controlled, multicenter trial (2015)
  • Author(s): F ukuda S, Koyama H, Kondo K, Fujii H, Hirayama Y, Tabata T, Okamura M, Yamakawa T, Okada S, Hirata S, Kiyama H, Kajimoto O, Watanabe Y, Inaba M, Nishizawa Y
  • Journal Title: PLoS ONE Volume: 10 Issue: 3 Pages: e0119578-e0119578
  • DOI: 10.1371/journal.pone.0119578
  • Peer Reviewed / Open Access
• [Journal Article] Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease. (2015)
  • Author(s): Nagata T, Kobayashi N, Ishii J, Shinagawa S, Nakayama R, Shibata N, Kuerban B, Ohnuma T, Kondo K, Arai H, Yamada H, Nakayama K.
  • Journal Title: Dementia and geriatric cognitive disorders extra Volume: 5(1) Pages: 64-73
  • Peer Reviewed
• [Journal Article] 疲労の尺度と疾病 (2015)
  • Author(s): 小林伸行, 近藤一博
  • Journal Title: 臨床透析 Volume: 5(1) Pages: 64-73
• [Presentation] 分子機構から明らかにする疲労とストレスとの相違に関する検討. (2017)
  • Author(s): 小林伸行, 岡直美, 髙橋麻弓, 玉井将人, 嶋田和也, 近藤一博.
  • Organizer: 第13回日本疲労学会
• [Presentation] 唾液中に分泌されたHHV-6がうつ病を発症させるメカニズムの解明 (2017)
  • Author(s): 岡直美、小林伸行、髙橋麻弓、嶋田和也、近藤一博
  • Organizer: 第13回日本疲労学会
• [Presentation] 疲労によって誘導されるウイルス因子が関与するうつ病発症メカニズムの解明 (2017)
  • Author(s): 岡直美、小林伸行、嶋田和也、髙橋麻弓、近藤一博
  • Organizer: 第39回生物学的精神医学会
• [Presentation] Human herpesvirus 6 (HHV-) and HHV-7 reactivation in fatigue, which distinguishes between physiological fatigue and pathological fatigue. (2016)
  • Author(s): Kobayashi, R.Aoki, H. Kuratsune, N. Oka, M.Takahashi, K. Shimada, W. Yamadera, M. Iwashita, H. Ito, K. Nakayama, K. Kondo.
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: Sapporo
  • Year and Date: 2016-10-23
• [Presentation] 疲労によって誘導されるウイルス因子が関与するうつ病発症メカニズムの解明 (2016)
  • Author(s): 岡直美、小林伸行、嶋田和也、髙橋麻弓、近藤一博
  • Organizer: 第38回生物学的精神医学会
  • Place of Presentation: 福岡
  • Year and Date: 2016-09-08
• [Presentation] 唾液中に分泌されたHHV-6がうつ病を発症させるメカニズムの解明 (2016)
  • Author(s): 岡直美、小林伸行、嶋田和也、髙橋麻弓、近藤一博
  • Organizer: 第12回日本疲労学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-05-20
• [Presentation] 唾液中ヒトヘルペスウイル ス(HHV-)6及びHHV-7量による病的疲労と生理的疲労と の鑑別に関する検討 (2016)
  • Author(s): 小林伸行, 青木亮, 岡直美, 髙橋麻弓 , 嶋田和也, 玉井将人, 山寺亘, 岩下正 幸, 倉恒弘彦, 伊藤洋, 中山和彦, 近藤 一博
  • Organizer: 第12回日本疲労学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-05-20
• [Presentation] Human Cytomegalovirus (HCMV) Latency-Associated Protein ORF152 Induces Calcium Influx and Inhibits Gene Expression in Central Nervous System (2015)
  • Author(s): Kazuya Shimada, Nobuyuki Kobayashi, Naomi Oka, Masato Tamai, Kazuhiro Kondo.
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2015-11-22
• [Presentation] 睡眠時無呼吸症候群を対象とした、HHV-6、HHV-7の再活性化メカニズムの検討 (2015)
  • Author(s): 小林伸行, 青木亮, 嶋田和也, 玉井将人, 山寺亘, 岩下正幸, 伊藤洋, 中山和彦, 近藤一博
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2015-11-22
• [Presentation] HCMV潜伏感染タンパク質ORF152が神経機能に与える影響 (2015)
  • Author(s): 嶋田和也、小林伸行、岡直美、玉井将人、近藤一博
  • Organizer: 第29回ヘルペスウイルス研究会
  • Place of Presentation: 長崎県長崎市
  • Year and Date: 2015-06-04