Adenovirus 36 seropositivity is related to the expression of anti-adipogenic lncRNAs GAS5 and MEG3 in adipose tissue obtained from subjects with obesity.

BACKGROUND: Human Adenovirus D-36 (HAdV-D36) promotes adipogenesis in cellular and animal models and may contribute to the development of human obesity. Induction of PPARγ by HAdV-D36 seems to have a central role in the maintenance of adipogenic status. There is limited information about epigenetic mechanisms contributing to this process in human adipose tissue. This study evaluated the expression of lncRNAs (ADINR, GAS5 and MEG3) and miRNAs (miR-18a and miR-140) involved in the adipogenic process in visceral adipose tissue (VAT) of subjects with obesity with previous HAdV-D36 infection (seropositive) and unexposed (seronegative) subjects with obesity. METHODS: Individuals with obesity were grouped according to the presence of antibodies against HAdV-D36 (Seropositive: HAdV-D36[+], n = 29; and Seronegative: HAdV-D36[-], n = 28). Additionally, a group of individuals without obesity (n = 17) was selected as a control group. The HAdV-D36 serology was carried out by ELISA. Biopsies of VAT were obtained during an elective and clinically indicated surgery (bariatric or cholecystectomy). RNA extraction from VAT was performed and the expression of PPARG and non-coding RNAs was evaluated by qPCR. RESULTS: HAdV-D36[+] individuals had lower expression of anti-adipogenic lncRNAs GAS5 (p = 0.016) and MEG3 (p = 0.035) compared with HAdV-D36[-] subjects with obesity. HAdV-D36[+] subjects also presented increased expression of the adipogenic miRNA miR-18a (p = 0.042), which has been reported to be modulated by GAS5 through a RNA sponging mechanism during adipogenic differentiation. Additionally, an inverse correlation of GAS5 with PPARG expression was observed (r = -0.917, p = 0.01). CONCLUSION: Our results suggest that HAdV-D36 is related to non-coding RNAs implicated in adipogenesis, representing a potential mechanism by which previous HAdV-D36 infection could be associated with the long-term maintenance of adipogenic status, probably through the GAS5/miR-18a axis.

Human Neutrophil Defensin-1, -3, and -4 Are Elevated in Nasal Aspirates from Children with Naturally Occurring Adenovirus Infection.

Background: Adenoviruses are highly contagious pathogens which cause respiratory disease particularly in children; they may induce severe disease in infants. Human neutrophil peptides (HNPs) have been found to exhibit antiadenoviral activity. Thus, we have investigated HNPs in nasal aspirates (NAs) of children suffering from adenoviral common cold. Objective: To investigate the release of HNP-1-4 in adenovirus infection and the relationship with self-limiting upper respiratory tract infections. Methods: Nasal aspirate samples (n=14) were obtained from children (aged 6-12 years) infected with adenovirus between June 2012 and December 2015. Control samples were taken 4 weeks after infection when the children were asymptomatic. Levels of HNPs were measured using an enzyme-linked immunosorbent assay (ELISA). Results: There were increased levels of HNP-1, -3, and -4, but not HNP-2, in nasal aspirates (NAs) during adenovirus infections compared to healthy specimens (p ≤ 0.01). Moreover, there was also increase in the neutrophil count, which is a known cell source of HNPs. Conclusion: Our finding supports the involvement of HNP-1, -3, and -4 in naturally occurring cold in children infected with adenovirus. Because of their known antiviral properties, it is tempting to hypothesize that HNPs might play a protective role in adenovirus-induced respiratory disease; however, this remains to be shown.