Cytomegalovirus seropositivity correlates with both human β-defensin 1 and IFN-γ downregulation in women with obesity

Obesity is characterized by a chronic systemic inflammation and a chronic low-grade inflammation in adipose tissue [1]. Obesity is associated with elevated levels of interleukins such as interferon-γ (IFN-γ), IL-5, IL-10, IL-12, IL-13 and TNF-α [2]. IFN-γ, also named type II, has potent antiviral properties. IFN-γ upregulates the human β-defensin-1 (hBD-1 peptide encoded by DEFB1 gene) levels. [3]. is a multifaceted antimicrobial peptide (AMP) with a role in allergic, inflammatory, neurologic diseases as well as cancer (reviewed in [4]). AMPs are one of the primordial arms of innate immunity. As antiviral, hBD-1 is active against Herpes Simplex Virus-1 (HSV-1, Hespesviridae)[5]. Infection by cytomegalovirus (CMV, Herpesviridae) can also produce chronic inflammation and is associated with obesity[6]. Herpesviruses such as HSV-1 downregulates hBD-1 levels [5] and certain haplotypes in DEFB1 gene have been associated with higher susceptibility to CMV [7]. However, in vitro or in vivo hBD-1 antiviral activity against CMV has not been tested (Gill Diamond, personal communication). Recently, it has been demonstrated that latent CMV infection adversely affects vaccine-induced responsiveness to SARS-CoV-2 spike protein [8] and CMV seropositivity is a novel risk factor for severe COVID-19 in non-geriatric (<60 years) patients[9]. CMV is also associated with high-density lipoprotein cholesterol levels [10]. The aim of this study was to determine whether the antiviral responses of both hBD-1 and IFN-γ correlate with hyperlipidemic (HDLc, TG), anthropometric or CMV index in groups of women with normal weight, overweight or obesity.

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