Scavenger receptor-mediated Ad5 entry and acLDL accumulation in monocytes/macrophages synergistically trigger innate responses against viral infection

• Published in: Virology (New York, N.Y.) Vol. 519; pp. 86 - 98
• Main Authors: Li, Pingchao, Feng, Fengling, Pan, Enxiang, Fan, Xiaozhen, Yang, Qing, Guan, Min, Chen, Ling, Sun, Caijun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2018
• Subjects: AcLDL accumulation; Adenoviridae; Adenoviridae infections; Adenovirus; antibodies; Infectious Disease; inflammation; Innate immunity; low density lipoprotein; macrophages; monocytes; pathogenesis; respiratory tract diseases; Scavenger receptor; serotypes; Scavenger receptor; AcLDL accumulation; Innate immunity; Adenovirus
• ISSN: 0042-6822; 1096-0341; 1096-0341
• DOI: 10.1016/j.virol.2018.04.005

Adenovirus serotype 5 (Ad5) is a common cause of respiratory tract infection, and populations worldwide have high prevalence of anti-Ad5 antibodies, implying extensively prior infection. Ad5 infection potently activates the host innate defense and inflammation, but the molecular mechanisms are not completely clarified. We report here that monocytes from Ad5-seropositive subjects upregulates the expression of scavenger receptor A (SR-A), and the increased SR-A promote the susceptibility of Ad5 entry and subsequent innate signaling activation. SR-A is also known as major receptor for lipid uptake, we therefore observed that monocytes from Ad5-seropositive subjects accumulated the acetylated low-density lipoprotein (acLDL) and had the elevated cellular stress to induce the activation of monocyte/macrophages. These findings demonstrate that SR-A-mediated Ad5 entry, innate signaling activation and acLDL accumulation synergistically trigger the robust antiviral innate and inflammatory responses, which are helpful to our understanding of the pathogenesis of adenovirus infection. •Monocytes from Ad5-seropositive subjects increase susceptibility to Ad5 infection;•The upregulated SR-A contributes to susceptibility of Ad5 entry into monocytes from Ad5-seropositive subjects;•SR-A-mediated acLDL accumulation and cellular stress occurs in monocytes from Ad5-seropositive subjects;•SR-A-mediated Ad5 entry, TLR3 activation and acLDL accumulation synergistically trigger antiviral innate responses;•A new mechanism for adenovirus-related innate immunity is demonstrated in this study.