CCCH-type zinc finger antiviral protein mediates antiviral immune response by activating T cells

Abstract

The zinc finger antiviral protein (ZAP), as a host restriction factor, inhibits the replication of certain viruses by binding viral mRNA or proteins for degradation. However, little is known about the role of ZAP in the antiviral immune response. We now show that ZAP participates in the antiviral immune response by activating T cells. Overexpression of ZAP significantly inhibited avian leukosis virus subgroup J (ALV-J) replication and reduced the associated inflammatory damage in vivo. In this study, we found that ZAP tended to be expressed in T lymphocytes, especially after ALV-J infection. T lymphocyte proliferation proceeded as usual in response to ALV-J infection in the presence of ZAP, indicating that ZAP endows T lymphocytes with resistance to the immunosuppression caused by ALV-J. Furthermore, ZAP activated cytokine secretion by T lymphocytes by contributing to nuclear translocation of nuclear factors of activated T cells and indirectly promoted anti-ALV-J antibody generation. Together, our findings show that ZAP, acting as an immunomodulatory factor, is involved in the antiviral immune response via T lymphocyte activation.

Targeted Restriction of Viral Gene Expression and Replication by the ZAP Antiviral System

“…During MLV infection, ZAP localizes to RNA granules with characteristics of both stress granules and processing bodies (23). ZAP also inhibits the deltaretrovirus human T-lymphotropic virus type-1 (HTLV-1) and the alpharetrovirus avian leukosis virus (35)(36)(37)(38). For both viruses, ZAP appears to target viral RNA transcripts for degradation.…”

Cytosine drives evolution of SARS‐CoV‐2

“…It may be relevant that the loops in stem‐loop sequences SL‐2 and SL‐3 of the viral 5′ region that are necessary for replication of the virus contain CpG motifs at the stem‐loop junction (Chen and Olsthoorn, ). As a third role of cytosine‐related functions, another unique involvement of CpG sequences rests in recognition of the viral sequence by the zinc‐finger antiviral protein (ZAP; Zhu et al ., ), which binds specifically to CpG viral sequences, recruiting multiple RNA degradation machines to degrade target viral RNA (Luo et al ., ). As a consequence of this antiviral response, CpG dinucleotides are suppressed in the genomes of many RNA viruses.…”

Host and Viral Zinc-Finger Proteins in COVID-19

“…ZNF family proteins can inhibit SARS-CoV-2 and increase host cellular defence through transcriptional regulation and act as antiviral effector proteins. ZNF transcription factors can activate type I interferon signalling and several antiviral genes [ 27 , 28 , 30 , 31 ], promote immune cells activation and maturation [ 32 , 33 ], but also directly or indirectly upturn the content of antiviral antibodies [ 33 , 34 ].…”