アフリカのゲノムからHIVを制御する方法を学ぶ(Learning how to control HIV from African genomes)

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2023-08-02 スイス連邦工科大学ローザンヌ校(EPFL)

◆EPFLのJacques Fellay教授らによる新しい研究では、HIVの自然な制御に関連する人間の遺伝子変異を探し出し、アフリカ系の集団でのみ存在する新しいゲノム領域を特定しました。
◆この研究により、CHD1L遺伝子が特定の白血球のサブセットでHIVの複製を制限する働きを持っていることが示されました。HIV感染の進行と感染力の決定因子であるsetpoint viral load(spVL)の制御に関する研究は、HIVに対する新しい治療法の可能性を示すものであり、特にアフリカ系の遺伝子多様性を考慮する重要性が強調されています。

<関連情報>

CHD1L近傍のアフリカ特有のヒト遺伝子変異がHIV-1感染量と関連 Africa-specific human genetic variation near CHD1L associates with HIV-1 load

Paul J. McLaren,Immacolata Porreca,Gennaro Iaconis,Hoi Ping Mok,Subhankar Mukhopadhyay,Emre Karakoc,Sara Cristinelli,Cristina Pomilla,István Bartha,Christian W. Thorball,Riley H. Tough,Paolo Angelino,Cher S. Kiar,Tommy Carstensen,Segun Fatumo,Tarryn Porter,Isobel Jarvis,William C. Skarnes,Andrew Bassett,Marianne K. DeGorter,Mohana Prasad Sathya Moorthy,Jeffrey F. Tuff,Eun-Young Kim,Miriam Walter,Lacy M. Simons,Arman Bashirova,Susan Buchbinder,Mary Carrington,Andrea Cossarizza,Andrea De Luca,James J. Goedert,David B. Goldstein,David W. Haas,Joshua T. Herbeck,Eric O. Johnson,Pontiano Kaleebu,William Kilembe,Gregory D. Kirk,Neeltje A. Kootstra,Alex H. Kral,Olivier Lambotte,Ma Luo,Simon Mallal,Javier Martinez-Picado,Laurence Meyer,José M. Miro,Pravi Moodley,Ayesha A. Motala,James I. Mullins,Kireem Nam,Niels Obel,Fraser Pirie,Francis A. Plummer,Guido Poli,Matthew A. Price,Andri Rauch,Ioannis Theodorou,Alexandra Trkola,Bruce D. Walker,Cheryl A. Winkler,Jean-François Zagury,Stephen B. Montgomery,Angela Ciuffi,Judd F. Hultquist,Steven M. Wolinsky,Gordon Dougan,Andrew M. L. Lever,Deepti Gurdasani,Harriet Groom,Manjinder S. Sandhu & Jacques Fellay
Nature  Published:02 August 2023
DOI:https://doi.org/10.1038/s41586-023-06370-4

アフリカのゲノムからHIVを制御する方法を学ぶ(Learning how to control HIV from African genomes)

Abstract

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.

細胞遺伝子工学
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