HIVの細胞間伝播は,抗レトロウイルス療法にもかかわらず,進行中の複製を可能にします

Alex Sigal¹, Jocelyn T Kim, Alejandro B Balazs

¹Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.

Nature

|August 19, 2011

まとめ

ヒト免疫不全ウイルス (HIV) の多細胞感染は,変異なしに薬剤の感受性を低下させる. 重要な感染経路である細胞間感染は,抗レトロウイルス治療中にHIVの複製を可能にし,治療を阻害する可能性がある.

科学分野:

ウイルス学ウイルス学ウイルス学
免疫学免疫学とは
薬理学薬理学とは

背景:

抗レトロウイルス療法 (ART) はヒト免疫不全ウイルス (HIV) の複製を抑制するが,薬剤無感性の貯蔵庫は残っている.
遅延と進行中の複製は,この持続的なHIV貯蔵庫のための提案されたメカニズムです.

研究の目的:

ART中に進行中のHIV複製のための新しいメカニズムを調査する.
細胞毎の複数の感染と細胞から細胞への拡散が,薬剤耐性への貢献をどのように探求する.

主な方法:

細胞毎の複数の感染が突然変異なしに薬剤感受性を低下させるモデルの実験的検証.
細胞から細胞へのHIV感染の薬物感受性の評価と,テノフォビルとエファヴィレンツの存在下で細胞フリーHIV感染の薬物感受性の評価.
ストキャスティック感染モデルを使用して,臨床薬剤濃度の下で,細胞から細胞に広がるHIVの複製を分析する.

主要な成果:

細胞毎の複数の感染は,薬剤耐性突然変異を必要とせずに,テノフォビルに対するHIVの感受性を低下させます.
HIVの細胞間感染は,細胞フリー感染と比較して,抗レトロウイルス薬テノフォビルとエファウィレンツに対して,著しく感受性が低い.
細胞間感染によるHIV複製は,臨床薬剤濃度の存在において,重大な変異の蓄積なしに,間接的に発生することがあります.

結論:

細胞毎の複数の感染と細胞から細胞への感染は,ARTの間に進行中のHIV複製の重要なメカニズムを表しています.
この伝播方式は,薬剤に対する感受性の低下につながり,治療の失敗を引き起こし,ウイルスの持続に寄与する可能性があります.
細胞間感染は,HIV感染を治すための障壁となり,免疫系に悪影響を及ぼす可能性があります.

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