Heindel Daniel W, Figueroa Acosta Dania M, Goff Marisa, Yengo Clauvis Kunkeng, Jan Muzafar, Liu Xiaomei, Wang Xiao-Hong, Petrova Mariya I, Zhang Mo, Sagar Manish, Barnette Phillip, Pandey Shilpi, Hessell Ann J, Chan Kun-Wei, Kong Xiang-Peng, Chen Benjamin K, Mahal Lara K, Bensing Barbara A, Hioe Catarina E
Divison of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Present address: Department of Biochemistry, Government Degree College Handwara, University of Kashmir, Jammu & Kashmir, India.
Res Sq. 2024 Jan 3:rs.3.rs-2596269. doi: 10.21203/rs.3.rs-2596269/v2.
Bacteria dysbiosis has been associated with an increased risk of HIV-1 transmission and acquisition. The prevalent idea is that bacteria dysbiosis compromises mucosal integrity and promotes inflammatory conditions to cause recruitment and activation of immune cells that harbor or are targeted by HIV-1. However, it is also possible that HIV-1 directly binds bacteria or bacterial products to impact virus infectivity and transmissibility. This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins. The Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated -linked glycans, was noted for its ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. Enhancing effects were recapitulated with -glycan-binding plant lectins, signifying the importance of -glycans. Conversely, -glycan-binding bacterial lectins FimH and Msl had no effect. SLBR-N was demonstrated to capture and transfer infectious HIV-1 virions, bind to -glycans on HIV-1 Env, and increase HIV-1 resistance to broadly neutralizing antibodies targeting different regions of Env. Hence, this study highlights the potential contribution of -glycans in promoting HIV-1 infection through the exploitation of -glycan-binding lectins from commensal bacteria at the mucosa.
细菌生态失调与HIV-1传播和感染风险增加有关。普遍的观点是，细菌生态失调会损害黏膜完整性并促进炎症状态，从而导致携带HIV-1或被HIV-1靶向的免疫细胞的募集和激活。然而，HIV-1也有可能直接结合细菌或细菌产物，从而影响病毒的感染性和传播性。本研究通过聚糖结合凝集素评估了HIV-1与细菌的相互作用。Siglec样凝集素SLBR-N是覆盖细菌表面的菌毛的一部分，可识别α2,3唾液酸化连接的聚糖，其在无细胞感染和细胞间转移的情况下增强HIV-1感染性的能力已得到关注。-聚糖结合植物凝集素也重现了增强作用，这表明-聚糖的重要性。相反，-聚糖结合细菌凝集素FimH和Msl则没有效果。已证明SLBR-N可捕获和转移具有传染性的HIV-1病毒粒子，与HIV-1 Env上的-聚糖结合，并增加HIV-1对靶向Env不同区域的广泛中和抗体的抗性。因此，本研究强调了-聚糖通过利用黏膜共生细菌的-聚糖结合凝集素在促进HIV-1感染中的潜在作用。
