➨14ᅇ䜏䛱䛾䛟䜴䜲䝹䝇ሿ

2015ᖺ7᭶18᪥-19᪥ி㒔኱Ꮫ䜴䜲䝹䝇◊✲ᡤᮅ㛗 ၨ㐀ி㒔኱Ꮫ䜴䜲䝹䝇◊✲ᡤ➨14ᅇ䜏䛱䛾䛟䜴䜲䝹䝇ሿி㒔኱Ꮫ䜴䜲䝹䝇◊✲ᡤᮅ㛗 ၨ㐀

2015ᖺ7᭶18᪥-19᪥

1956ᖺタ❧”䜴䜲䝹䝇”䛾ྡ䛜௜䛔䛯၏୍䛾኱Ꮫ㝃ᒓ◊✲ᶵ㛵ி㒔኱Ꮫ䜴䜲䝹䝇◊✲ᡤ➨14ᅇ䜏䛱䛾䛟䜴䜲䝹䝇ሿ

2015ᖺ7᭶18᪥-19᪥䛂䜴䜲䝹䝇䛾᥈✲୪䜃䛻䜴䜲䝹䝇⑓䛾ண㜵ཬ䜃἞⒪䛻㛵䛩䜛Ꮫ⌮ཬ䜃䛭䛾ᛂ⏝䛾◊✲䛃ி㒔኱Ꮫ䜴䜲䝹䝇◊✲ᡤᮅ㛗 ၨ㐀䛂䜴䜲䝹䝇ឤᰁ⑕䜈䛾⌮ゎ䜢䛥䜙䛻῝䜑䜛䛯䜑䚸⣽⬊䛭䛧䛶ಶయ䝺䝧䝹䛷䛾⏕࿨⌧㇟䛾ㅦ䜢ゎ䛝᫂䛛䛩◊✲䛃䝪䝹䝘䜴䜲䝹䝇䠖㐍໬䜢ඹ䛻䛧䛯ෆ䛺䜛䜴䜲䝹䝇

6/87/19/348/2,290┠㻛⛉㻛ள⛉㻛ᒓ㻛✀
Fields Virology, 6th ed., 2013

10,000,000,000,000,000,000,000,000,000,000䜴䜲䝹䝇⢏Ꮚ

Hamilton G, Nature 2006ே䞉ື≀䞉᳜≀䛻⑓Ẽ䜢㉳䛣䛩䜴䜲䝹䝇䛯䛱z ⑌ᝈඞ᭹z ⑓ཎᛶ䛾ゎ᫂z 㜵␿యไ☜❧z ண㜵ἲ䛾ᶞ❧z 䝽䜽䝏䞁⑓Ẽ䛸䛿㛵ಀ䛺䛔䜴䜲䝹䝇䛯䛱z ච␿ຊz ⣽⳦ឤᰁ䜈䛾ᑐᛂz ᰾㓟䠄DNA/RNA䠅zzzzᮍ▱䛾⑓Ẽ᪂⯆䜴䜲䝹䝇䜈䛾ᑐᛂ䜴䜲䝹䝇ከᵝᛶ┘どయไ

VIRUS WORLD

longhorndave
http://www.flickr.com/photos/davidw/2297
191644/⤯⁛䜴䜲䝹䝇ྂ䜴䜲䝹䝇Ꮫ䠄Paleovirology)ྂ䜴䜲䝹䝇Ꮫ㐣ཤ䛾䜴䜲䝹䝇ឤᰁ䜢▱䜚䚸㐍໬㐣⛬䛻䛚䛡䜛⏕≀䛸䜴䜲䝹䝇䛸䛾㛵䜟䜚䠄ඹᏑ䞉➇⏕䠅䜢᥈䜛⤯⁛䜴䜲䝹䝇?

⤯⁛䜴䜲䝹䝇

⚾䛯䛱䛾య䛾୰䛻䛒䜛

䝀䝜䝮DNA᰾䚸ᰁⰍయ䚸DNA
ᰁⰍయ

DNA⚾䛯䛱䛾䝀䝜䝮DNA䛻䛿䜴䜲䝹䝇⏤᮶䛾᰾㑇ఏ᝟ሗ䛜ᩘከ䛟Ꮡᅾ䛧䛶䛔䜛

....GCATCGAGTCCAACGTAGCTAGCTAGCTTTTAGCTAGCTGGACCCCATTTTTACGATAGTAAA.....
....CGTAGCTCAGGTTGCATCGATCGATCGAAAATCGATCGACCTGGGGTAAAAATGCTATCATTT.....

䝀䝜䝮DNA䠄㑇ఏ᝟ሗ䠅䜴䜲䝹䝇䛻⏤᮶䛩䜛㑇ఏ᝟ሗෆᅾᛶ䜴䜲䝹䝇Endogenous Viruses㐣ཤ䛻ឤᰁ䛧䛯䜴䜲䝹䝇䛾⑞㊧䠄䜴䜲䝹䝇໬▼䠅䛺䛬䚸⚾䛯䛱⏕≀䛾䝀䝜䝮䛻䛿䜴䜲䝹䝇䛻⏤᮶䛩䜛䝀䝜䝮㓄ิ᝟ሗ䛜Ꮡᅾ䛧䛶䛔䜛䛾䛛䠛䛒䜛≉Ṧ䛺䜴䜲䝹䝇ឤᰁ䛧䛯ᐟ୺⏕≀䛾䝀䝜䝮DNA䛻⮬䜙䛾䝀䝜䝮䜢⤌䜏㎸䜐䛣䛸䛷」〇䛩䜛

䜴䜲䝹䝇」〇䜴䜲䝹䝇DNA

䜲䞁䝔䜾䝺䞊䝅䝵䞁䠄ᤄධ䠅ᐟ୺䝀䝜䝮DNAz 䝺䝖䝻䜴䜲䝹䝇
RNA㏫㌿෗㓝⣲DNARNA䜴䜲䝹䝇䛾ෆᅾ໬⏕Ṫ⣽⬊ᤄධ䠄䜲䞁䝔䜾䝺䞊䝅䝵䞁䠅ឤᰁ⪅ᩓⓎᛶ㠀ᅛᐃ໬㠀㑇ఏᛶෆᅾ໬䛜⏕Ꮡ䛻᭷฼኱ὶ⾜ᅛᐃ໬ෆᅾ໬⚾䛯䛱䛾䝀䝜䝮DNA䛾ఱ%䛜
ෆᅾᛶ䜴䜲䝹䝇䛺䛾䛛䠛ෆᅾᛶ䜴䜲䝹䝇

HUMAN GENOME
Exons (1.5%)ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇, LTR䝺䝖䝻䝖䝷䞁䝇䝫䝌䞁 (8%)
㐣ཤ䛻䛚䛡䜛䝺䝖䝻䜴䜲䝹䝇ឤᰁ䛾⑞㊧z ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇: 98,000 䜶䝺䝯䞁䝖z LTR䝖䝷䞁䝇䝫䝌䞁: 158,000 䜶䝺䝯䞁䝖Others, including
introns (42.5%)

LINE (22%)

㠀LTR䝺䝖䝻䝖䝷䞁䝇䝫䝌䞁

Satellites, including
telomeres (5%)

SINE, Alu (16%)
DNA transposons(3.5%)ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇z ⚾䛯䛱䛿㐍໬䛾㐣⛬䛷䝺䝖䝻䜴䜲䝹䝇䛾⇿Ⓨⓗ䛺ὶ⾜䜢ఱᗘ䛸䛺䛟⤒㦂䛧䛯z 䜴䜲䝹䝇ឤᰁ䛿⚾䛯䛱䛾㐍໬䛾኱䛝䛺᥎㐍ຊෆᅾᛶ䜴䜲䝹䝇⚾䛯䛱⏕≀䛾”ᡂ䜚❧䛱”䛾ㅦ䜢䜂䜒ゎ䛟㔜せ䛺せ⣲ෆᅾᛶ䜴䜲䝹䝇◊✲z 1964z 䝔䝭䞁䛾DNA䝥䝻䜴䜲䝹䝇௬ㄝz Late 1960s
z Early 1970sz 1974z 1981z 1995
䡚 1988z 2007z 2008z 2009z 2010Dr. Howard M. Temin

1975ᖺ:䝜䞊䝧䝹⏕⌮Ꮫ䞉་Ꮫ㈹䛂⭘⒆䜴䜲䝹䝇䛸㑇ఏᏊ䛸䛾┦஫స⏝䛻㛵䛩䜛◊✲䛃
(1934䠉1994)

1964ᖺ䛻䚸䛂RNA⭘⒆䜴䜲䝹䝇䛿DNA䛻ኚ᥮䛥䜜䛶䚸ᐟ୺ᰁⰍయ䛻ྲྀ䜚㎸䜎䜜䜛㐣⛬䜢௓䛧䛶ቑṪ䛩䜛䛃䛸䛔䛖DNA䝥䝻䜴䜲䝹䝇௬ㄝ䜢ᥦၐ䚹䛣䜜䛿䚸DNA䛛䜙RNA䛜䛴䛟䜙䜜䜛䛸䛔䛖䛭䜜䜎䛷䛾⏕≀Ꮫ䛾䝉䞁䝖䝷䝹䝗䜾䝬䛻┿䛳ྥ䛛䜙ᑐ䛩䜛䜒䛾䛷䛒䛳䛯䛯䜑䚸ᙜึ䛿඲䛟ཷ䛡ධ䜜䜙䜜䛺䛛䛳䛯䚹䛧䛛䛧䛺䛜䜙䚸1970ᖺ䛻ධ䜚䚸㗪ᆺRNA䛛䜙DNA䜢స䜚ฟ䛩㓝⣲䛾୍✀䛷䛒䜛
䇾㏫㌿෗㓝⣲䇿䜢⮬䜙Ⓨぢ䛩䜛䛣䛸䛷௬ㄝ䛾ṇ䛧䛥䜢ド᫂䛧䛯䚹䝜䞊䝧䝹㈹䛿䝔䝭䞁䛸䛿ಶู䛻㏫㌿෗㓝⣲䜢Ⓨぢ䛧䛯David Baltimore䛜ྠ᫬ཷ㈹䛧䛶䛔䜛䚹DNA䝥䝻䜴䜲䝹䝇௬ㄝRNA⭘⒆䜴䜲䝹䝇䠄䝷䜴䝇⫗⭘䜴䜲䝹䝇䠖RSV䠅䜴䜲䝹䝇䛺䛧䛜䜣㑇ఏᏊ䠄src䠅⒴໬
䜴䜲䝹䝇䛒䜚

䜴䜲䝹䝇䛜䛔䛶䜒䛔䛺䛟䛶䜒⒴໬ᛶ≧䛜⥔ᣢ䠄䜴䜲䝹䝇䛾⑓ཎᛶ䛜㑇ఏ䛧䛶䛔䜛䟿䠅DNA」〇䜢Ṇ䜑䜛⸆䜴䜲䝹䝇䛾」〇䛜㜼ᐖ䛥䜜䛯䜴䜲䝹䝇䛒䜚⣽⬊ឤᰁ⣽⬊ෆ䛷RNA䜴䜲䝹䝇䛜DNA
䛸䛧䛶Ꮡᅾ䛧䛶䛔䜛
Temin HM: Nature of the provirus of Rous sarcoma. Nat Cancer Inst Monogr 1964, 17:557-570.

DNA䝥䝻䜴䜲䝹䝇௬ㄝRNA⭘⒆䠄䝺䝖䝻䠅䜴䜲䝹䝇䛿DNA䛻ኚ᥮䛥䜜䛶䚸ᐟ୺ᰁⰍయ䛻ྲྀ䜚㎸䜎䜜䜛㐣⛬䜢௓䛧䛶ቑṪ䛩䜛ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾᥈⣴⏕≀䛾䝀䝜䝮䛻䛿䝺䝖䝻䜴䜲䝹䝇䛻⏤᮶䛩䜛㑇ఏᏊ᩿∦䛜Ꮡᅾ䛧䛶䛔䜛䛛䜒䛧䜜䛺䛔䠛ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾Ⓨぢ䝙䝽䝖䝸ⓑ⾑⑓䜴䜲䝹䝇䠖ALV1960’s ⱥᅜᢠయ䠇䜴䜲䝹䝇ᢠయ䛸ᢠཎ䛾᳨ᰝ䜴䜲䝹䝇䠇ᢠయ䠉䜴䜲䝹䝇䠇ឤᰁ䛧䛯䛣䛸䛾䛺䛔㫽䛻䜴䜲䝹䝇䛾䝍䞁䝟䜽㉁䛜䛒䜛
ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾Ⓨぢ䝷䜴䝇⫗⭘䜴䜲䝹䝇䠖RSVAgagpolBgagpolenv

᏶඲䛺㑇ఏᏊ䠄⮬ᕫ」〇ྍ⬟䠅୙᏶඲䛺㑇ఏᏊ䠄⮬ᕫ」〇୙ྍ⬟䠅AA」〇Bb?

୙᏶඲䛺䜴䜲䝹䝇㑇ఏᏊ䜢⿵䛖䛣䛸䛜䛷䛝䜛㑇ఏᏊ䛜䛒䜛ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾Ⓨぢឤᰁ䛧䛯䛣䛸䛾䛺䛔㫽䛻䜴䜲䝹䝇䛾䝍䞁䝟䜽㉁䛜䛒䜛
୙᏶඲䛺䜴䜲䝹䝇㑇ఏᏊ䜢⿵䛖䛣䛸䛜䛷䛝䜛㑇ఏᏊ䛜䛒䜛
Spontaneous virus production from "non-virus producing" Roussarcoma cells.
Weiss RA.
Virology. 32(4):719-23. (1967)
The heritable nature of the factor in chicken cells which acts as ahelper virus for Rous sarcoma virus.
Weiss RA, Payne LN.
Virology. 45(2):508-15. (1971)⏕≀䛾㑇ఏᏊ䛾୰䛻䝺䝖䝻䜴䜲䝹䝇䛻⏤᮶䛩䜛㑇ఏᏊ䛜Ꮡᅾ䛧䛶䛔䜛ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾Ⓨぢ᪥ᮏே䛾ά㌍A type of chick embryo cell that fails to
support formation of infectious RSV.
Hanafusa T, Miyamoto T, Hanafusa H.
Virology. 40:55-64 (1970)ⰼᡣ⚽୕㑻䠄⡿ᅜ䝻䝑䜽䝣䜵䝷䞊኱Ꮫྡ㄃ᩍᤵ䠅
1929 - 2009ᖺ1950 ᖺ ኱㜰኱Ꮫ⌮Ꮫ㒊໬Ꮫ⛉ධᏛ1958 ᖺ ኱㜰኱Ꮫᚤ⏕≀⑓◊✲ᡤຓᡭ
1961 ᖺ ⡿ᅜ䜹䝸䝣䜷䝹䝙䜰኱Ꮫ䜴䜲䝹䝇◊✲ᡤ◊✲ဨ
1964 ᖺ ௖ᅜ䝁䝺䝑䝆䞉䝗䞉䝣䝷䞁䝇ᐇ㦂་Ꮫ◊✲ᐊ◊✲ဨ1966 ᖺ ⡿ᅜ䝙䝳䞊䝶䞊䜽බ⾗⾨⏕◊✲ᡤ⒴䜴䜱䝹䝇◊✲㒊㛗
1973 ᖺ ⡿ᅜ䝻䝑䜽䝣䜵䝷䞊኱Ꮫᩍᤵ䠄ศᏊ⭘⒆Ꮫ䠅1986 ᖺ ⡿ᅜ䝻䝑䜽䝣䜵䝷䞊኱Ꮫ Leon Hess Professor
1998 ᖺ ⡿ᅜ䝻䝑䜽䝣䜵䝷䞊኱Ꮫྡ㄃ᩍᤵ ኱㜰䝞䜲䜸䝃䜲䜶䞁䝇◊✲ᡤᡤ㛗့ங㢮䛷䛾ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾ⓎぢAKR䝬䜴䝇㐜Ⓨᛶ䛾ⓑ⾑⑓䜴䜲䝹䝇⢏Ꮚ䛜ᨺฟ䛥䜜䛯䟿ᇵ㣴⣽⬊䜢స〇Mouse leukemia virus: "spontaneous" release bymouse embryo cells after long-term in vitro
cultivation.
Aaronson SA, Hartley JW, Todaro GJ.
Proc Natl Acad Sci U S A. 64:87-94. (1969)ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾ⓎぢAKR䝬䜴䝇䛾ⓑ⾑⑓䛾Ⓨ⑕ᶵᗎ

Bedigian HG, Shultz LD, Meier H.
Nature 279:434-436. (1979)⏕ᚋ䛩䛠䛻ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䜢స䜚ฟ䛩␗䛺䜛✀㢮䛾」〇୙᏶඲ᆺෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛸⤌᥮䛘䜢㉳䛣䛩యෆ䛷⤌䜏᥮䛳䛯䜴䜲䝹䝇䛜ⓑ⾑⑓䜢ᘬ䛝㉳䛣䛩ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛾Ⓨぢᢠయ⏘⏕⬟ຊ䛜పୗ䛧䛶䛔䜛ಶయ䛷䛿ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛜άᛶ໬䛧䛶䚸⑓ཎᛶ䛾䛒䜛䜴䜲䝹䝇䜢స䜚ฟ䛩䚹䛜䜣ᝈ⪅䚸⮬ᕫච␿⑌ᝈᝈ⪅䚸ච␿୙඲⑕ᝈ⪅䛷䜒ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇䛜άᛶ໬䛧䛶䛔䜛ෆᅾᛶ䜴䜲䝹䝇䛾Ⓨぢz 1964z 䝔䝭䞁䛾DNA䝥䝻䜴䜲䝹䝇௬ㄝz Late 1960sz Early 1970sz ෆᅾᛶ䝖䝸ⓑ⾑⑓䜴䜲䝹䝇 (ALV)z ෆᅾᛶ䝬䜴䝇ⓑ⾑⑓䜴䜲䝹䝇 (MLV)z ෆᅾᛶ䝬䜴䝇ங䜺䞁䜴䜲䝹䝇 (MMTV)(Weiss RA et al., Vogt PK et al., Hanafusa et al., Varmus EV et al., Aaronson SA et al. ...)

z 1974z ෆᅾᛶ㟋㛗㢮䝺䝖䝻䜴䜲䝹䝇z 1981z 䝠䝖ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇(BaEV)(HERVs)༢⣧䝺䝖䝻䜴䜲䝹䝇(Martin MA et al.)z 1995
䡚 1988z ෆᅾᛶMLV䛾◊✲䛻ᚑ஦z 2007z 2008z 2009z 䜴䝃䜼ෆᅾᛶ䝺䞁䝏䜴䜲䝹䝇 (RELIK)z 2010䠄⡿ᅜ䝪䝇䝖䞁䞉䝬䝃䝏䝳䞊䝉䝑䝒䠅z 䝠䝶䜿䝄䝹ෆᅾᛶ䝺䞁䝏䜴䜲䝹䝇 (PSIVgml)z 䝘䝬䜿䝰䝜ෆᅾᛶ 䝣䜷䞊䝭䞊䜴䜲䝹䝇」㞧䝺䝖䝻䜴䜲䝹䝇␲ၥ⏕≀䝀䝜䝮䛻䛿䝺䝖䝻䜴䜲䝹䝇௨እ䛾ෆᅾᛶ䜴䜲䝹䝇䛿ᮏᙜ䛻Ꮡᅾ䛧䛺䛔䛾䛛?

䜒䛧Ꮡᅾ䛩䜜䜀ෆᅾᛶ䜴䜲䝹䝇◊✲䞉ྂ䜴䜲䝹䝇Ꮫ䛾ᙉຊ䛺Ṋჾ䛻䛺䜛ෆᅾᛶ䜴䜲䝹䝇䛾Ⓨぢz 1964z 䝔䝭䞁䛾DNA䝥䝻䜴䜲䝹䝇௬ㄝz Late 1960sz Early 1970sz ෆᅾᛶ䝖䝸ⓑ⾑⑓䜴䜲䝹䝇 (ALV)z ෆᅾᛶ䝬䜴䝇ⓑ⾑⑓䜴䜲䝹䝇 (MLV)z ෆᅾᛶ䝬䜴䝇ங䜺䞁䜴䜲䝹䝇 (MMTV)(Weiss RA et al., Vogt PK et al., Hanafusa et al., Varmus EV et al., Aaronson SA et al. ...)

z 1974z ෆᅾᛶ㟋㛗㢮䝺䝖䝻䜴䜲䝹䝇z 1981z 䝠䝖ෆᅾᛶ䝺䝖䝻䜴䜲䝹䝇(BaEV)(HERVs)༢⣧䝺䝖䝻䜴䜲䝹䝇(Martin MA et al.)z 1995
䡚 1988z ෆᅾᛶMLV䛾◊✲䛻ᚑ஦z 2007z 2008
z 2009z 䜴䝃䜼ෆᅾᛶ䝺䞁䝏䜴䜲䝹䝇 (RELIK)z 2010䠄⡿ᅜ䝪䝇䝖䞁䞉䝬䝃䝏䝳䞊䝉䝑䝒䠅z 䝠䝶䜿䝄䝹ෆᅾᛶ䝺䞁䝏䜴䜲䝹䝇 (PSIVgml)z 䝘䝬䜿䝰䝜ෆᅾᛶ 䝣䜷䞊䝭䞊䜴䜲䝹䝇」㞧䝺䝖䝻䜴䜲䝹䝇z 䝺䝖䝻䜴䜲䝹䝇௨እ䛾䜴䜲䝹䝇໬▼䜢䝠䝖䜢ྵ䜐့ஙື≀䛷Ⓨぢෆᅾᛶ䜴䜲䝹䝇䛾Ⓨぢ2010z Jan.

 䝪䝹䝘䜴䜲䝹䝇(Horie et al., Nature)z Jun.

 䝣䜱䝻䜴䜲䝹䝇(Taylor et al., BMC Evol Biol.)z Jul.

 䝣䜱䝻䜴䜲䝹䝇 䝭䝑䝗䜴䜵䜲䜴䜲䝹䝇(Belyi et al., PLoSPathogen)z Sep.

 䝦䝟䝗䝘䜴䜲䝹䝇(Gilbert et al., PLoS Biology)(Belyi et al., J. Virol.)z Oct.

 䝟䝹䝪䜴䜲䝹䝇(Kapoor et al., J. Virol.)z Nov.

 䝤䞁䝲䜴䜲䝹䝇 䝷䝤䝗䜴䜲䝹䝇(Katzourakis et al., PLoS Genetics)

 䝕䝨䞁䝗䜴䜲䝹䝇(Liu et al., J. Virol.)2011
z Jul.

 䝟䝹䝪䜴䜲䝹䝇 䝃䞊䝁䜴䜲䝹䝇 RNA virus DNA virus
 RT-DNA virus⚾䛯䛱䛾䝀䝜䝮䛻䛿䛣䜜䜎䛷⪃䛘䜙䜜䛶䛔䛯௨ୖ䛻䜴䜲䝹䝇⏤᮶䛾㓄ิ䛜ྲྀ䜚㎸䜎䜜䛶䛔䜛ෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇䛾⏕≀㐍໬䛸䜴䜲䝹䝇Ꮫ䜈䛾ព⩏䝪䝹䝘䜴䜲䝹䝇
Bornavirus䝪䝹䝘䜴䜲䝹䝇
X3’NGPM

L5’୍ᮏ㙐䝬䜲䝘䝇㙐RNA䜴䜲䝹䝇GMLPgRNARNP

N37䝰䝜䝛䜺䜴䜲䝹䝇┠ 䝟䝷䝭䜽䝋䜴䜲䝹䝇 䝷䝤䝗䜴䜲䝹䝇Ź 㯞⑈䜴䜲䝹䝇Ź ≬≟⑓䜴䜲䝹䝇Ź 䝮䞁䝥䝇䜴䜲䝹䝇Ź 䝸䝑䝃䜴䜲䝹䝇 䝣䜱䝻䜴䜲䝹䝇 䝪䝹䝘䜴䜲䝹䝇Ź 䜶䝪䝷䜴䜲䝹䝇Ź 䝪䝹䝘⑓䜴䜲䝹䝇Ź 䝬䞊䝹䝤䝹䜾䜴䜲䝹䝇Ź 㫽䝪䝹䝘䜴䜲䝹䝇䝪䝹䝘⑓z 17ୡ⣖ᚋ༙䜘䜚䠈䝗䜲䝒༡ᮾ㒊䛾䜴䝬䛷☜ㄆ䛥䜜䛶䛔䛯㢼ᅵ⑓䠄䜴䝬⇕⬻⑕ 䠅䠊z ⚄⤒䞉㐠ືჾ㞀ᐖ䠄␗ᖖ⯆ዧ䠈↓ື䠈ỿ䛖䛴䠈Ṍ⾜␗ᖖ䛺䛹䠅䜢♧䛩⑌ᝈ䠊z 1885ᖺ䠈䝗䜲䝒ᮾ㒊䛾⏫䝪䝹䝘䛻䛚䛔䛶䜴䝬䛷኱ὶ⾜䠊

Borna෗┿䠖㮵ඣᓥ኱Ꮫ ᇼỤ┿⾜Ặᥦ౪䝪䝹䝘⑓z ᚤ⇕䚸⾜ື␗ᖖ䚸▱ぬ㐣ᩄ䚸↓㛵ᚰ䛺䛹䛾⑕≧䛜ㄆ䜑䜙䜜䡠②ᨥ䚸↓ື䚸㯞⑷䛺䛹䜢࿊䛧䛯ᚋ䚸඲㌟㯞⑷䛻㝗䜚䚸⣙80%䛜Ṛஸ.
z 㠀໬⮋ᛶ㧊⭷⬻⅖䠊䝸䞁䝟⌫䜢୰ᚰ䛸䛩䜛ᅖ⟶ᛶ⣽⬊ᾐ₶䚸䜾䝸䜸䞊䝅䝇䜢♧䛩.

http://www.vetscite.org/publish/articles/000106/index.html

䝪䝹䝘⑓୰ኸ⋇་఍㞧ㄅ(1898)䝪䝹䝘⑓୰ኸ⋇་఍㞧ㄅ (1932)䝪䝹䝘⑓䝗䜲䝒ὶ⾜ᆅ䛷䛾Ⓨ⑕㢌ᩘ䠄䜴䝬䠅ே䛸䝪䝹䝘⑓䜴䜲䝹䝇
Science 1985 May 10;228(4700):755-6.

• ୡ⏺ⓗ䛺␿Ꮫㄪᰝ• 䜴䜲䝹䝇Ꮫⓗᇶ♏◊✲• ᅜ㝿䝅䞁䝫䝆䜴䝮• ཌປ┬◊✲⌜1985-1998ᖺ䝪䝹䝘⑓䜴䜲䝹䝇䛾␿Ꮫ䝪䝹䝘⑓䜴䜲䝹䝇䛾␿Ꮫ◊✲ᑐ㇟⑌ᝈ䛾୙ᆒ୍ᛶ᳨ฟ᪉ἲ䛾୙Ᏻᐃ䛥ศ㞳䜴䜲䝹䝇ᰴ䛾୙☜䛛䛥⤖ᯝ䛻ಙ㢗ᛶ
䛜䛺䛔䝪䝹䝘䜴䜲䝹䝇◊✲ື≀䛾⑓Ẽὶ⾜ᅜ௨እ䛻䛿ឤᰁ䛿䛺䛔ே䜈䛾⑓ཎᛶ䛿㝈䜚䛺䛟᛹䛧䛔ឤᰁ⋡䛿䛝䜟䜑䛶ప䛔

9 බ⾗⾨⏕ୖ඲䛟ၥ㢟䛺䛔
9 䝽䜽䝏䞁䜔἞⒪ἲ䛾㛤Ⓨ䛿ᚲせ䛺䛔9 ◊✲㈝䜒ᚲせ䛺䛔䝪䝹䝘䜴䜲䝹䝇◊✲ື≀䛾⑓Ẽὶ⾜ᅜ௨እ䛻䛿ឤᰁ䛿䛺䛔ே䜈䛾⑓ཎᛶ䛿㝈䜚䛺䛟᛹䛧䛔ឤᰁ⋡䛿䛝䜟䜑䛶ప䛔

9 ㄡ䜒䜴䜲䝹䝇䛾ᐇែ䜢▱䜙䛺䛔
9 ⊂⮬䛾䝃䜲䜶䞁䝇䜢ᒎ㛤䛷䛝䜛䝪䝹䝘䜴䜲䝹䝇◊✲䝪䝹䝘䜴䜲䝹䝇䛾䜴䜲䝹䝇Ꮫ䛸⚄⤒⑓ཎᛶ᰾ෆᣢ⥆ឤᰁᶵᵓ䛾ゎ᫂䝪䝹䝘䜴䜲䝹䝇䛾฼⏝ෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇䛾ព⩏䛸ඹ㐍໬䝠䝖⑓ཎᛶ䝪䝹䝘䜴䜲䝹䝇䛾᥈⣴䝠䝖⑓ཎᛶ䝪䝹䝘䜴䜲䝹䝇䠄వㄯ䠅ෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇䛾ⓎぢBDV RNP䛿ศ⿣ᮇᰁⰍయ䛻⧅䛞䛸䜑䜙䜜䛶䛔䜛SIMゎᯒanaphase䠄ᚋᮇ䠅RNP

BDV NDAPI500 nm

BDV RNP䛿⣽⬊ศ⿣ᮇ䛻䛚䛔䛶ᰁⰍయ䛸୍య䛸䛺䜚Ᏻᐃ໬䛧䛶䛔䜛ෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇Bornavirus
LOC340900
LOC55096

1 MPPKRR---LVDDADAMEDQDLYEPPASLPKLPGKFLQYTVGGSDPHPGIGHEKDIRQNAVALLDQSRRDMFHTVTPSLV 77
1 MSRPRNNPQTSSPQDSTKDGSSFHYFQGRFELSGKSRQYPADALEPQPGIGDVKVIEKATKSMLDPAQRSHFYLVTPSLV 80
1 MSHLRKDSQPSSPGDDAMDRSGLPDLQGRFELSGKNRQYPLDALEPQPSIGDIKDIKKAAKSMLDPAHKSHFHPVTPSLV 8078 FLCLLIP GLHAAFVHGGVPRESYLSTPVTRGE-QTVVKTAKFYGEKTTQRDLTELEISSIFSHCCSLLIGVVIGSSSKIK 156
81 FLCFIFDGLHKALLSVGVSKRSNIVIGNENKETGTLYAS-KFED---VLPTFTALEMSSILRHCCD-LIGIAAGSSDPIC 155
81 FLCFIFDGLHQALLSVGVSKRSNTVVGNENEERGTPYAS-RFKD----MPNFIALEKSSVLRHCCDLLIGIAAGSSDKIC 155
157 AGAEQIKKRFKTMMAALNRPSHGETATLLQMFNPHEAIDWINGQPWVGSFVLSLLTTDFESPGKEFMDQIKLVASYAQMT 236
156 TNSLQVQRQFKAMMISIGRPLHSESADLLISYNAGPAIDWINSRPWVGGLMFTFLFGEFESPACELLDQVKVVASKAQMM 235156 TSSLQVQRRFKAMMASIGRLSHGESADLLISCNAESAIGWISSRPWVGELMFTLLFGDFESPLTQAT-QVKLVAKKAQMT 234
237 TYTTIKEYLAECMDATLTIPVVAYEIRDFLEVSAKL-KEDHADLFPFLGAIRHPDAIKLAPRSFPNLASAAFYWSKKENP 315SATAANYWAKRRNS 314
236 TYYTVRMFLDQCVDGSTALPAVVLEIPVF-EQKKPLAKKVLGDFFEFGGVLRHPVIGVLSPQMFPNLSATAANYWAKMSNP 312
235 TY-CVRMFLDQCMDGSIALRAIVSEIPVF-EEKKTMVKKALGKYFEFGGVLCHPIIGELSPRMFPNL316 TMAGYRASTIQPGASVKETQLARYRRRE -ISRGEDGAELSGEISAIMKMIGVTGLN
315 TFSGFEALDIIPG-STITFPVLQMASAQKISRGSDMDPYTLNILRGYGISG FE - -313 TFLGFKAPDVIPG-STITLPLLQMASPRKILRGECWVESIHALLTTNSHYLK- - --370366363

ෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇Bornavirus genome structure

X
N

3’
S1

GP

M

S2

S3

T1

T2

L

5’

Signalsequences
T3

T5

T4Consensus
LOC340900
LOC55096

(i)

(ii)

Transcription initiation :Translation termination :Chr. 10Chr. 3GAA(N)CAAT(A)6-7

S1(i) BDV N
LOC340900
LOC55096

Termination codon(ii) BDV N
LOC340900
LOC55096

Start codon

TTAACAACAAACCACTCATCATTCTTCTAACAAAATGAACACACGCAATGCCATAGTACAGTACAAAATTGTGTGAAAATCACAGAAACAATCACCCACAATGTCCTGATTCTTAACAAAATTAAAGAATTAAGTCGGAACCAATTTTCCACAATGTCTS2T1AACTAAAAAACAATGAACAAACCAATAAAAAACCAAATGCGGCAAACCCTCCGGAATAACAAATACGTGAACTAATCCTTATATATACATATAAAAAGAAATTATG
GCACTCCTAACATGAACTAATTCTCATTATTTAAAAAAAAAAAAAAAAAAAAAෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇䝪䝹䝘䜴䜲䝹䝇䝀䝜䝮AAAAAAAA䜴䜲䝹䝇mRNAsAAAAAAAA

LINE-1 䝺䝖䝻䝖䝷䞁䝇䝫䝌䞁ᐟ୺DNAEBLs
Horie et al. Nature (2010)

EBLsEndogenous bornavirus-like elementsෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇ᵝ㓄ิෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇ᵝ㓄ิ 䠄EBLs䠅䝠䝖ᰁⰍయෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇ᵝ㓄ิ 䠄EBLs䠅

Horie et al., Philos. Trans. R. Soc. Lond.-B Biol. Sci. (2013)

EBL䛿䛔䛴䝀䝜䝮䛻ᤄධ䛥䜜䛯䛛䠛4,000-4,500୓ᖺ๓

Primates
Indian python
Aye ayeMouse lemur
Afrotheria

8,300୓ᖺ๓
2,000୓ᖺ๓

Afrotheria
Rodents
Cape golden moleStar-nosed mole
Guniea pig

BDV30୓ᖺ๓௨㝆

EBLN tree < E-20
Amino acids
Bootstrap value > 70%

Thirteen-lined ground squirrel

ABV

Suzuki et al. Genes Genet. Syst. (2014)
Kobayashi et al. Unpublished dataෆᅾᛶ䝪䝹䝘䜴䜲䝹䝇ᵝᅉᏊ䠄EBL䠅䛾≉ᚩ

EBL• 䛭䜜䛮䜜䛾✀䛿ᩘ䝁䝢䞊䠄ከ䛟䛿10ಶ௨ୗ䠅䛾EBL䜢䝀䝜䝮䛻ᣢ䛴• ᩘ༓୓ᖺ㛫ORF䜢ಖᣢ䛧䛶䛔䜛EBL䛜䛒䜛• ከ䛟䛾EBLᗙ䛿RNA䛸䛧䛶㌿෗䛥䜜䛶䛔䜛䠊䛭䛾䛖䛱䛔䛟䛴䛛䛿䝍䞁䝟䜽㉁䛻
⩻ヂ䛥䜜䛶䜛.
• EBL䜢䝀䝜䝮䛻䜒䛴ື≀✀䛿ẚ㍑ⓗ
BDVឤᰁ䛻ᑐ䛧䛶᢬ᢠᛶ䜢♧䛩䠊EBL䛸BDV⑓ཎᛶ䛾┦㛵ᛶᐟ୺
Anthropoids
Prosimian
Mouse/Rat
Squirrel
Guinea pig
Dog
Cat
Horse
Cow
RabbitSheepPig
Shrew
Opossum
Birds

EBLs

⮬↛ឤᰁ㻛⑌ᝈ䠇䠇䠇䠇䠇䞊䞊䞊䞊䞊䞊䞊䠇䠇䞊䠇㻛 䞊
ND㻛ND
䞊㻛 䞊
ND㻛ND䞊㻛 䞊䠇㻛 䠇䠇㻛 䠇䠇㻛 䠇䠇㻛 䠇䠇㻛 䠇䠇㻛 䠇
ND㻛ND䠇㻛 䞊䠇㻛 䠇䠉䠇㻛 䠇
ND; not determinedEBL䛾ㅦ

EBL䛻䛿ᢠ䜴䜲䝹䝇ᶵ⬟䛜䛒䜛?
EBLs+୙㢧ᛶឤᰁ䞉ప⑓ཎᛶ

EBLs䝪䝹䝘䜴䜲䝹䝇⮴Ṛᛶ⑌ᝈ

EBL䛾ㅦ

EBL䛻䛿ᢠ䜴䜲䝹䝇ᶵ⬟䛜䛒䜛?

ᐟ୺⣽⬊䛻䛚䛡䜛EBL䛾ᶵ⬟ゎ᫂䝆䝳䜴䝃䞁䝉䞁䝆䝸䝇䠄TLS䠅䝀䝜䝮⏤᮶EBL
itEBLN

Fujino et al. Proc. Nat. Acad. Sci. USA (2014)

TLS EBL (itEBLN)
BDV䝀䝜䝮XNGPMLTLS 䝀䝜䝮BDV N
itEBLNBDV N䛸䛾䜰䝭䝜㓟┦ྠᛶ = 77%

itEBLN䛾Ⓨ⌧

Suzuki et al., Gen Genet Syst. (2014)

Fujino et al. Proc. Nat. Acad. Sci. USA (2014)⤌᥮䛘itEBLN䛾ᵓ⠏䜴䜱䝇䝁䞁䝅䞁኱Ꮫ䜸䝅䝳䝁䝅䝳ᰯ

EBLs

BDV NHAHA

itEBLN
N-itEBLN

HAᑟධ

BDVឤᰁ⣽⬊

⤌᥮䛘itEBLN䛾⣽⬊ෆᒁᅾ

Fujino et al. Proc. Nat. Acad. Sci. USA (2014)

itEBLN䛾Ⓨ⌧䛿BDVឤᰁ䜢㜼ᐖ䛩䜛
itEBLNᏳᐃⓎ⌧䝠䝖ᰴ໬⣽⬊+GFPⓎ⌧⤌᥮䛘BDVឤᰁVero⣽⬊itEBLN䛻䜘䜛BDV」〇䛾㜼ᐖBDV᰾vRNP䜈䛾ྲྀ䜚㎸䜏

itEBLNX

X

RNPX⣽⬊㉁

itEBLN䛿BDV RNP䛻ྲྀ䜚㎸䜎䜜䚸䝗䝭䝘䞁䝖䝛䜺䝔䜱䝤ኚ␗య䛸䛧䛶」〇䜢㜼ᐖ䛧䛶䛔䜛.

䝬䜴䝇䠄Mus musculus䠅䝀䝜䝮⏤᮶EBLsmmEBLNs

Parrish et al. (in press)

mmEBLNs
1370

Bornavirus Nucleoprotein

50370

Chr 11mmEBLN-1

100367

Chr 11mmEBLN-250370

Chr 18mmEBLN-350327

Chr 6mmEBLN-4218

Chr 9274mmEBLN-5

ഇ㑇ఏᏊ໬䛧䛶䛔䜛䝬䜴䝇⢭ᕢ䛻䛚䛡䜛mmEBLN⏤᮶పศᏊRNA䛾Ⓨ⌧
1370

Bornavirus Nucleoprotein¥50370Chr 11mmEBLN-1

100367

Chr 11mmEBLN-2

¥ 370

50

Chr 18mmEBLN-350327

Chr 6mmEBLN-4218

Chr 9¥mmEBLN-5274

mmEBLN䛿䝟䜻䝔䞁ᮇpiRNA䜢Ⓨ⌧䛧䛶䛔䜛

25-31nt hit reads Total reads
E16 testis
74791433
10 days-old testis03522097
6 weeks-old testis3632
14630696
GS cells
09670728

Sense
0Antisense
703632

Collaboration with Dr. Nakano & Kuramochi-Miyagawa

piRNA (Piwi-interacting RNA)z ୺䛻⏕Ṫ⣽⬊䛷Ⓨ⌧䛧䛶䛔䜛పศᏊ䛾䝜䞁䝁䞊䝕䜱䞁䜾RNA.
z Piwi䠄Miwi䠅䛸RNP䜢ᙧᡂ䛧䛶⏕Ṫ⣽⬊䛻䛚䛡䜛䝺䝖䝻䝖䝷䞁䝇䝫䝌䞁䛾㌿⛣䜢䜶䝢䝆䜵䝛䝔䜱䜽䛻䛒䜛䛔䛿㌿෗ᚋ䝃䜲䝺䞁䝅䞁䜾䛻䜘䜚ᢚไ䛧䛶䛔䜛䠊z య⣽⬊䛻䛚䛡䜛piRNA䛾Ⓨ⌧䛸㑇ఏᏊᢚไ䛾ᙺ๭䜒♧၀䛥䜜䛶䛔䜛.
z ከ䛟䛾piRNA䛿piRNA clusters䛸࿧䜀䜜䜛1䛛䜙100kb䛾㛗䛥䛾㡿ᇦ䛻䝁䞊䝗䛥䜜䛶䛔䜛.

mmEBLN䛿piRNA cluster䛻䝁䞊䝗䛥䜜䛶䛔䜛

EBLᗙ䛛䜙䛾piRNA䛾Ⓨ⌧piRNA䜽䝷䝇䝍䞊䛻EBL䛜⵳✚䛩䜛☜❧ (P)3/5 EBLNs within piRNA cluster

p = 8 x 10-5

p = 1 x 10-6

p = 4.5 x 10-5

p = 0.008

EBL䛾⮬↛㑅ᢥ
EBLN-piRNA㱎ṑ㢮䛸㟋㛗㢮䛾♽ඛ䛻䛚䛔䛶䛿䚸piRNA䜽䝷䝇䝍䞊
䛻EBL䛜⤌䜏㎸䜎䜜䛯✀䛜㑅ᢥⓗ䛻ṧ䛳䛶䛝䛯ྍ⬟ᛶ䛜⪃䛘䜙䜜䜛䠊Mus musculus

Homo sapiens

EBL-piRNA௬ㄝෆᅾ໬ឤᰁῈử?

4,500୓ᖺ๓

X

EBLs in piRNAcluster

ឤᰁῈử?

X

2,000୓ᖺ๓

EBLs in piRNAcluster

EBL-piRNA௬ㄝ䜴䜲䝹䝇mRNAs䜰䞁䝏䝀䝜䝮RNA

EBL-piRNAs

AAAAAAAAAAAAAAAA㌿෗ᚋ㑇ఏᏊᢚไ
EBL⏤᮶piRNA䛜䝪䝹䝘䜴䜲䝹䝇䛾ឤᰁ䛒䜛䛔䛿᪂つෆᅾ໬䜢㜼ᐖ䛧䛶䛔䜛?

䜴䜲䝹䝇ឤᰁ䛻㛵୚䛩䜛ෆᅾᛶ䜴䜲䝹䝇ᅉᏊ
EDI

Viral origin/host genome

Function(s)Fv4

Retroviral env/mouse

Receptor interference

endogenous JSRV

Betaretroviral gag; env/sheep

Heteromultimerization, receptor
interference

endogenous FeLV

Retroviral env/cat

Receptor interference

endogenous ALV

Avian leukosis virus env;
whole/chicken

Receptor interference, immune
tolerization

IRIS

env/fruit fly

Unknown

Rmcf1, 2

env/mouse

Receptor interference

Fv1

Retroviral gag/mouse

Capsid interaction

Gypsy-like LTR retrotransposons

Retroviral gag/vertebrates

Unknownendogenous MMTV

Mouse mammary tumor virus
sag/mouse

T cell deletion

EBLN

Bornavirus-like NP/mammalianUnknown

NIRVs

Ebolavirus-like VP35; NP/Bats

Unknown

CGIN1

Retroviral RNase/mammalian

APOBEC3

Retroviral regulatory element

IAPV

Picornavirus

Unconfirmed ubiquitination
mechanism
Up regulation of viral inhibition byAPOBEC
Unknown

Trends in Ecology &amp; Evolution Volume 27, Issue 11 2012 627 - 636䜴䜲䝹䝇䛸ᐟ୺䛾ඹ㐍໬

<AB<<A+ෆᅾ໬䠄ᐙ␆໬䠅᢬ᢠᛶඹᏑ⚾䛯䛱䛾䝀䝜䝮䛾୰䛻䛿㐣ཤ䛻ឤᰁ䛧䛯䜴䜲䝹䝇䛻ᑐ䛩䜛᢬ᢠᛶ䛾グ᠈䛜╀䛳䛶䛔䜛䜴䜲䝹䝇ෆᅾ໬䛾᪂䛧䛔ᴫᛕ⚾䛯䛱䛿㐍໬㐣⛬䛻䛚䛔䛶䜴䜲䝹䝇ឤᰁ䜢⮬ศ䛯䛱䛾䝀䝜䝮䛾୍㒊䛸䛧䛶グ᠈䛧䚸✀䛾⏕Ꮡ䜔㐍໬䛻฼⏝䛧䛶䛝䛯䠊ឤᰁグ᠈