Human endogenous retroviruses in viral disease and therapy

Abstract

As retained sequences of ancient retroviruses, human endogenous retroviruses (HERVs) are widespread in the human genome. Although most HERVs have been inert throughout evolution, several HERVs are still functional and involved in various diseases, such as autoimmune diseases, cancer, neurological diseases and viral infection. Hence, certain types of therapies targeting HERVs or utilizing HERV tools have been developed. Here, we summarize recent findings on the role of HERVs in viral infection, including HERV dysregulation in different kinds of viral infections and the potential mechanisms of HERV‐mediated antiviral immunity. In addition, we provide an overview of HERV‐related therapies that directly target HERVs or are indirectly based on HERVs to improve the efficacy of vaccines and drugs.

Antiviral activity of the human endogenous retrovirus‐R envelope protein against SARS‐CoV‐2

“…Many HERVs also induce the expression of interferon‐stimulated genes (ISGs), thus activating the antiviral innate immune response pathways (Li et al , 2022). HERV‐K activates NF‐kB, cGAS (cyclic GMP‐AMP), and STING (cyclic GMP‐AMP receptor stimulator of interferon genes) signaling pathways (Li et al , 2022).…”

“…Many HERVs also induce the expression of interferon‐stimulated genes (ISGs), thus activating the antiviral innate immune response pathways (Li et al , 2022). HERV‐K activates NF‐kB, cGAS (cyclic GMP‐AMP), and STING (cyclic GMP‐AMP receptor stimulator of interferon genes) signaling pathways (Li et al , 2022). HERVs are also implicated in many viral infections, including DNA viruses (such as KSHV, HSV‐1, HCMV, and EBV), RNA viruses (hepatitis C virus, dengue virus, influenza virus, and SARS‐CoV‐2), and retroviruses (HIV‐1 and HTLV) (Sutkowski et al , 2001; Contreras‐Galindo et al , 2006; Assinger et al , 2013; Bhardwaj et al , 2014; Bergallo et al , 2015; Dai et al , 2018; Tovo et al , 2020; Wang et al , 2020; Balestrieri et al , 2021; Bello‐Morales et al , 2021; Kitsou et al , 2021).…”

Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2

“…Many HERVs induce the expression of interferon-stimulated genes (ISGs), thus activating the antiviral innate immune response pathways (Li et al, 2022). HERV-K activates NF-kB, cGAS (cyclic GMP-AMP) and STING (cyclic GMP-AMP receptor stimulator of interferon genes) signaling pathways (Li et al, 2022).…”

“…Many HERVs induce the expression of interferon-stimulated genes (ISGs), thus activating the antiviral innate immune response pathways (Li et al, 2022). HERV-K activates NF-kB, cGAS (cyclic GMP-AMP) and STING (cyclic GMP-AMP receptor stimulator of interferon genes) signaling pathways (Li et al, 2022). HERVs are also implicated in many viral infections, including DNA viruses (such as KSHV, HSV-1, HCMV, EBV), RNA viruses (Hepatitis C Virus, Dengue virus, Influenza virus, SARS-CoV-2) and retroviruses (HIV-1, HTLV) (Dai et al,2018; Bello-Morales et al, 2021; Assinger et al,2013; Bergallo et al, 2015; Sutkowski et al, 2001; Tovo et al, 2020; Kitsou et al, 2021; Balestrieri et al, 2021; Bhardwaj et al, 2020; Contreras-Galindo et al, 2006; Wang et al, 2020).…”