Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads and its replication in cell culture

Abstract

BackgroundThe human immunodeficiency virus (HIV-1) exploits host proteins to complete its life cycle. Genome-wide siRNA approaches suggested that host proteins affect HIV-1 replication. However, the results barely overlapped. RING finger protein 39 (RNF39) has been identified from genome-wide association studies. However, its function during HIV-1 replication remains unclear.Methods and resultsWe investigated the relationship between common RNF39 genetic variants and HIV-1 viral loads. The effect of RNF39 protein knockdown or overexpression on HIV-1 replication was then investigated in different cell lines. Two genetic variants were associated with HIV-1 viral loads. Patients with the ht1-GG/GG haplotype presented lower RNF39 expression levels and lower HIV-1 viral load. RNF39 knockdown inhibited HIV-1 expression.ConclusionsRNF39 protein may be involved in HIV-1 replication as observed in genetic studies on patients with HIV-1 and in in vitro cell cultures.

Identification of key genes and pathways associated with cholangiocarcinoma development based on weighted gene correlation network analysis

“…RNF39 encoded a member of ring finger proteins, which was studied in Behcets disease, a chronic inflammatory autoimmune disease (Kurata et al, 2010). In addition, RNF39 protein was suggested to participate in the replication process according to both studies on HIV-1 individuals and cell-lines (Lin et al, 2014). PRSS56 has been established as an effective marker of adult neurogenesis in the brain of mouse (Jourdon et al, 2016).…”

Emerging Roles of MHC Class I Region-Encoded E3 Ubiquitin Ligases in Innate Immunity

“…The DNA methylation state of RNF39 impacts autoimmune disorders, including MS, SLE and allergic rhinitis (AR, a delayed hypersensitivity nasal mucosa reaction to environmental allergens, caused by IgE mediated release of autacoids) and confers poor responsiveness to HBV vaccination (69)(70)(71)(72). Furthermore, RNF39 genetic variants are related to HIV-1 plasma viral loads, CD4 + T cell count, and the clinical course of HIV-1 infection (73)(74)(75). Besides its role in DNA viruses and retrovirus infection, RNF39 has also been identified as a feedback suppressor of RNA virus-induced signaling and antiviral immunity.…”

RNF39 mediates K48-linked ubiquitination of DDX3X and inhibits RLR-dependent antiviral immunity

“…Previous genome-wide association studies have mapped to a region close to the RNF39 associated with HIV-1 disease progression ( 21 ). Plasma HIV-1 viral loads are associated with RNF39 genetic variants in patients infected with HIV-1, and RNF39 inhibits cellular HIV-1 replication ( 22 ). However, the biological function of RNF39 in antiviral responses remains unknown.…”

“…RING finger protein 39 (RNF39; also called HZFw), which contains a RING domain and has potential E3 ubiquitin ligase activity, is also encoded within the MHC class I region (20). Genetic variant of RNF39 is associated with a variety of viral diseases and autoimmune diseases, such as HIV, multiple sclerosis (MS), Behcet's disease, allergic rhinitis, and systemic lupus erythematosus (SLE) (21)(22)(23)(24)(25)(26)(27). Previous genome-wide association studies have mapped to a region close to the RNF39 associated with HIV-1 disease progression (21).…”