Author:
Giron Leila B,Liu Qin,Adeniji Opeyemi S,Yin Xiangfan,Kannan Toshitha,Ding Jianyi,Lu David Y.,Langan Susan,Zhang Jinbing,Azevedo Joao L. L. C.,Li Shuk Hang,Shalygin Sergei,Azadi Parastoo,Hanna David B,Ofotokun Igho,Lazar Jason,Fischl Margaret A.,Haberlen Sabina,Macatangay Bernard,Adimora Adaora A.,Jamieson Beth D.,Rinaldo Charles,Merenstein Daniel,Roan Nadia R.,Kutsch Olaf,Gange Stephen,Wolinsky Steven,Witt Mallory,Post Wendy S.,Kossenkov Andrew,Landay Alan,Frank Ian,Tien Phyllis C.,Gross Robert,Brown Todd T.,Abdel-Mohsen Mohamed
Abstract
ABSTRACTPeople with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging-associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence-associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic-based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.
Publisher
Cold Spring Harbor Laboratory