Farina Iole, Andreotti Mauro, Pastori Claudia, Bona Roberta, Galluzzo Clementina Maria, Amici Roberta, Purificato Cristina, Uberti-Foppa Caterina, Riva Agostino, Gauzzi Maria Cristina, Lopalco Lucia, Fantuzzi Laura
National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Virus Res. 2024 Dec;350:199506. doi: 10.1016/j.virusres.2024.199506. Epub 2024 Dec 9.
CCR5 is the main co-receptor for HIV-1 cell entry and it plays key roles in HIV-1 mucosal transmission. Natural anti-CCR5 antibodies were found in HIV-1-exposed seronegative and long-term non-progressor subjects, suggesting a role in controlling viral replication in vivo. We assessed the effect of sera containing or not natural anti-CCR5 antibodies, on membrane CCR5 level and HIV-1 infection in primary macrophages. Sera modulated CCR5 expression with a trend dependent on the donor/serum tested but independent on the presence or absence of anti-CCR5 antibodies. All sera strongly reduced HIV-1 DNA in all donor's macrophages and no correlation was observed between CCR5 and viral DNA levels. These results suggest that CCR5 expression level is not a major determinant of macrophage infection and that the observed modulation of CCR5 and HIV-1 DNA might depend on factors other than CCR5-reactive antibodies present in sera and/or intrinsic to the donors on which sera were tested.
CCR5是HIV-1进入细胞的主要共受体,在HIV-1黏膜传播中起关键作用。在暴露于HIV-1的血清阴性和长期不进展者体内发现了天然抗CCR5抗体,提示其在体内控制病毒复制中发挥作用。我们评估了含有或不含天然抗CCR5抗体的血清对原代巨噬细胞中膜CCR5水平和HIV-1感染的影响。血清调节CCR5表达,其趋势取决于所检测的供体/血清,但与抗CCR5抗体的有无无关。所有血清均显著降低了所有供体巨噬细胞中的HIV-1 DNA,且未观察到CCR5与病毒DNA水平之间存在相关性。这些结果表明,CCR5表达水平不是巨噬细胞感染的主要决定因素,且观察到的CCR5和HIV-1 DNA的调节可能取决于血清中存在的CCR5反应性抗体以外的因素和/或所检测血清供体固有的因素。