Basic study on HIV-1 replication and pathogenicity in host individuals: functional analysis of accessory proteins

• Project/Area Number: 26293104
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: The University of Tokushima
• Principal Investigator: ADACHI Akio 徳島大学, 大学院医歯薬学研究部, 特命教授 (90127043)
• Co-Investigator(Kenkyū-buntansha): 野間口 雅子 徳島大学, 大学院医歯薬学研究部, 准教授 (80452647) ; 宮崎 恭行 徳島大学, 大学院医歯薬学研究部, 助教 (70607233)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: ウイルス / HIV-1 / HIV-1rmt / アクセサリー蛋白質 / アカゲザル / 抗HIV-1因子 / SIV / HIV-1mt

Outline of Final Research Achievements

It is critically important to establish the rhesus/viral infection system to elucidate HIV-1 replication and pathogenicity in host individuals. We have made every effort to generate CCR5- and rhesus macaque-tropic HIV-1 (HIV-1rmt) clones that grow enough to cause persistent infection and finally induce AIDS. We have successfully obtained molecular HIV-1rmt clones that grow equally or better in rhesus cells relative to the best-growing CXCR4-tropic HIV-1rmt previously described. We thus have advanced to the rhesus-infection experiments to functionally analyze HIV-1 accessory proteins.

Research Products

• [Journal Article] Expression profiles of Vpx/Vpr proteins are co-related with the primate lentiviral lineage. (2016)
  • Author(s): Sakai, Y., Miyake, A., Doi, N., Sasada, H., Miyazaki, Y., Adachi, A, and Nomaguchi, M.
  • Journal Title: Frontiers in Microbiology Volume: 7 Pages: 1211-1211
  • DOI: 10.3389/fmicb.2016.01211
  • NAID: 120006937686
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phylogenetic insights into the functional relationship between primate lentiviral reverse transcriptase and accessory proteins Vpx/Vpr. (2016)
  • Author(s): Sakai, Y., Doi, N., Miyazaki, Y., Adachi, A, and Nomaguchi, M.
  • Journal Title: Frontiers in Microbiology Volume: 7 Pages: 1655-1655
  • DOI: 10.3389/fmicb.2016.01655
  • NAID: 120006937687
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Natural single-nucleotide variations in the HIV-1 genomic SA1prox region can alter viral replication ability by regulating Vif expression levels. (2016)
  • Author(s): Nomaguchi, M., Doi, N., Sakai, Y., Ode, H., Iwatani, Y., Ueno, T., Matsumoto, Y., Miyazaki, Y., Masuda, T., and Adachi, A.
  • Journal Title: Journal of Virology Volume: 90 Pages: 4563-4578
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel mutant human immunodeficiency virus type 1 strains with high degree of resistance to cynomolgus macaque TRIMCyp generated by randam mutagenesis. (2016)
  • Author(s): Sultana, T., Nakayama, E.E., Tobita, S., Yokoyama, M., Seki, Y., Saito, A., Nomaguchi, M., Adachi, A., Akari, H., Sato, H., and Shioda, T.
  • Journal Title: Journal of General Virology Volume: 97 Issue: 4 Pages: 963-976
  • DOI: 10.1099/jgv.0.000408
  • Peer Reviewed / Open Access
• [Journal Article] Single-amino acid mutation 66SR in Gag-matrix enhances viral single-cycle infectivity of R5-tropic HIV-1rmt. (2015)
  • Author(s): Doi, N., Sakai, Y., Miyazaki, Y., Adachi, A., and Nomaguchi, M.
  • Journal Title: Journal of Medical Investigation Volume: 62 Pages: 228-232
  • NAID: 130005099140
  • Peer Reviewed
• [Journal Article] In silico analysis of HIV-1 Env-gp120 reveals structural bases for viral adaptation in growth-restrictive cells. (2015)
  • Author(s): Yokoyama, M., Nomaguchi, M., Doi, N., Kanda, T., Adachi, A., and Sato, H.
  • Journal Title: Frontiers in Microbiology Volume: 7
  • DOI: 10.3389/fmicb.2016.00110
  • NAID: 120006937684
  • Peer Reviewed / Open Access
• [Journal Article] Animal model studies on viral infections. (2014)
  • Author(s): Adachi, A., and Miura, T.
  • Journal Title: Frontiers in Microbiology Volume: 5 Pages: 672-672
  • DOI: 10.3389/fmicb.2014.00672
  • Peer Reviewed / Open Access
• [Journal Article] Distinct combinations of amino acid substitutions in N-terminal domain of Gag-capsid afford HIV-1 resistance to rhesus TRIM5α. (2014)
  • Author(s): Nomaguchi M, Nakayama EE,Yokoyama M, Doi N,Igarashi T, Shioda T, Sato H, Adachi A.
  • Journal Title: Microbes and Infection Volume: 16 Issue: 11 Pages: 936-944
  • DOI: 10.1016/j.micinf.2014.08.017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Growth properties of macaque-tropic HIV-1 clones carrying <i>vpr/vpx </i>genes derived from simian immunodeficiency viruses in place of their <i>vpr </i>regions (2014)
  • Author(s): Doi, N., Adachi, A., and Nomaguchi, M.
  • Journal Title: The Journal of Medical Investigation Volume: 61 Issue: 3.4 Pages: 374-379
  • DOI: 10.2152/jmi.61.374
  • NAID: 130004822744
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] Virological characterization of HIV-2 vpx gene mutants in various cell systems. (2014)
  • Author(s): Nomaguchi, M., Doi, N., and Adachi, A.
  • Journal Title: Microbes and Infection Volume: 16 Issue: 8 Pages: 695-701
  • DOI: 10.1016/j.micinf.2014.06.004
  • Peer Reviewed / Open Access
• [Journal Article] Natural single-nucleotide polymorphisms in the 3' region of HIV-1 pol gene modulate viral replication ability. (2014)
  • Author(s): Nomaguchi, M. Miyake, A., Doi, N., Fujiwara, S., Miyazaki, Y., Tsunetsugu-Yokota, Y., Yokoyama, M., Sato, H., Masuda, T., and Adachi, A.
  • Journal Title: Journal of Virology Volume: 88 Issue: 8 Pages: 4145-4160
  • DOI: 10.1128/jvi.01859-13
  • Peer Reviewed / Open Access
• [Presentation] Effects of mutations HIV-1 Gag-CA helix 7 and linker domain on the virion production. (2016)
  • Author(s): Fujimoto, K., Doi, N., Sakai, Y., Adachi, A., and Nomaguchi, M.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道札幌市)
  • Year and Date: 2016-10-23
• [Presentation] An ultra-low vif type of HIV-1 SA1D2prox variant can adapt and evolve under the high level of APOVEC3G. (2016)
  • Author(s): Adachi, A., Doi, N., Sakai, Y., Fujimoto, K., and Nomaguchi, M.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道札幌市)
  • Year and Date: 2016-10-23
• [Presentation] Identification of cis-elements involved in the HIV-1 vif mRNA production. (2016)
  • Author(s): Nomaguchi, M., Doi, N., Fujimoto, K., Sakai, Y., Nakanishi, S., and Adachi A.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道札幌市)
  • Year and Date: 2016-10-23
• [Presentation] Replication and pathogenicity of HIV-1rmt: towards evaluation of viral growth ability in gut-derived cells. (2016)
  • Author(s): Doi, N., Ishifune, C., Yasutomo, K., Miura, T., Sakai, Y., Fujimoto, K., Harada, S., Yoshimura, K., Nomaguchi, M., and Adachi, A.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道札幌市)
  • Year and Date: 2016-10-23
• [Presentation] Studies on the adaptation process of HIV-1 Env in macaque cells. (2016)
  • Author(s): Sakai, Y., Fujimoto, K., Doi, N., Nomaguchi, M., and Adachi, A.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道札幌市)
  • Year and Date: 2016-10-23
• [Presentation] Novel mutant human immunodeficiency virus type 1 strains with high degree of resistance to cynomolgus macaque TRIMCyp generated by random mutagenesis. (2016)
  • Author(s): Sultana, T., Nakayama, E.E., Tobita, S., Yokoyama, M., Seki, Y., Saito, A., Nomaguchi, M., Adachi, A., Akari, H., Sato, H., Shioda, T.
  • Organizer: The 23rd Conference on Retroviruses and Opportunistic Infections
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-02-22
  • Int'l Joint Research
• [Presentation] SA1proxの1塩基置換によるHIV-1 Vif発現量変動機構 (2015)
  • Author(s): 野間口雅子、土肥直哉、吉田知哉、酒井遥介、宮崎恭行、足立昭夫
  • 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（福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] HIV-1 Vif発現量を増減させるSA1D2prox塩基配列の同定 (2015)
  • Author(s): 足立昭夫、土肥直哉、酒井遥介、吉田知哉、宮崎恭行、野間口雅子
  • 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（福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] CCR5-tropic アカゲザル指向性HIV-1の構築とウイルス学的性状解析 (2015)
  • Author(s): 土肥直哉、野間口雅子、酒井遥介、足立昭夫
  • 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（福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] HIV-1 Gag-CA I134/I135/S149の1アミノ酸変異はウイルス複製後期過程に影響する (2015)
  • Author(s): 酒井遥介、土肥直哉、宮崎恭行、足立昭夫、野間口雅子
  • 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（福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] Novel mutant HIV-1 strains with high degree of resistance to cynomolgus macaque TRIMCyp generated by random mutagenesis. (2015)
  • Author(s): Sultana, T., Nakayama, E.E., Tobita, S., Saito, A., Nomaguchi, M., Adachi, A., Akari, H., Shioda, T.
  • Organizer: The 63rd Annual Meeting of The Japanese Society for Virology
  • Place of Presentation: Fukuoka International Congress Center (Fukuoka, Fukuoka)
  • Year and Date: 2015-11-22
• [Presentation] 抗HIV細胞因子と抗HIV戦略. (2014)
  • Author(s): 足立昭夫
  • Organizer: 第28回日本エイズ学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市）
  • Year and Date: 2014-12-05
• [Presentation] In vitro構築系を用いたHIV-1/HIV-2 CA重合能に関する解析. (2014)
  • Author(s): 宮崎恭行、泉泰輔、野間口雅子、内山恒夫、足立昭夫
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市）
  • Year and Date: 2014-11-11
• [Presentation] HIV-1 Cag-CAへリックス7の変異がウイルス複製後期過程に及ぼす影響の解析. (2014)
  • Author(s): 土肥直哉、宮崎恭行、酒井遥介、泉泰輔、内山恒夫、足立昭夫、野間口雅子
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市）
  • Year and Date: 2014-11-11
• [Presentation] SA1proxの遺伝子配列はVif/APOBEC3G依存的にウイルス複製能を変動させる. (2014)
  • Author(s): 野間口雅子，土肥直哉、酒井遥介、泉泰輔、宮崎恭行、足立昭夫
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-11-10
• [Presentation] HIV/SIV Vpx蛋白質の発現調節に寄与する領域の解析. (2014)
  • Author(s): 酒井遥介、笹田ひかり、土肥直哉、泉泰輔、宮崎恭行、足立昭夫、野間口雅子
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市）
  • Year and Date: 2014-11-10