Functional Involvement of Interferon-Inducible Transmembrane Proteins in Antiviral Immunity

Abstract

Interferons (IFNs) play crucial roles in host defense against viral infections by inducing the expression of numerous IFN-stimulated genes (ISGs) that can activate host antiviral immunity. Interferon-inducible transmembrane proteins (IFITMs), a family of small transmembrane proteins, are critical ISG products. Compelling evidence has implicated that IFITMs can establish an innate immune state to eliminate pathogens efficiently. IFITM proteins can impede broad-spectrum viral infection through various mechanisms. It is generally believed that IFITMs can block the viral entry by suppressing viral membrane fusion. However, some findings indicated that IFITMs might also inhibit viral gene expression and viral protein synthesis and thereby impair viral replication. IFITMs may incorporate into virions during viral assembly and thus reduce the infectivity of nascent virions. The precise inhibitory mechanism of IFITMs on viral infection and replication still requires further exploration. In this review, we highlight the recent findings regarding critical roles of IFITMs in host-virus interaction. We also discuss the molecular mechanisms underlying their functions in antiviral responses.

Interferon-Independent Innate Responses to Cytomegalovirus

“…IFITM proteins are also implicated in the antiviral response against a wide range of viruses: orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses often by blocking membrane fusion (127,(138)(139)(140). However, overexpression of IFITM1, IFITM2 and IFITM3 does not inhibit HCMV infection but rather results in a modest increase in the percentage of infected cells (141,142).…”

The IFITM protein family in adaptive immunity

“…The family of interferon-inducible transmembrane (Ifitm/ Fragilis) genes encode small homologous proteins localized in the plasma and endolysosomal membranes, which can confer cellular resistance to many viruses in both mice and humans. [1][2][3] The IFITM family were first discovered as interferon-induced genes in human neuroblastoma cells and their promoters contain one or more interferon-stimulated response elements, making them responsive to type I and type II interferons. [4][5][6][7] However, IFITM expression can be regulated independently of interferon signalling.…”

Porcine IFITM1 is a host restriction factor that inhibits pseudorabies virus infection

“…In addition, IFN-inducible transmembrane proteins (IFITMs) are a group of antiviral restriction factors that act against a broad range of viruses [13], such as influenza A virus [14], human immunodeficiency virus (HIV)-1 [15], West Nile virus and dengue virus [16], vesicular stomatitis virus [17], severe acute respiratory syndrome coronavirus and Marburg virus [18], classical swine fever virus [19] and African swine fever virus [20]. The mechanisms by which IFITMs influence virus infection are restriction of viral entry, viral assembly or viral protein synthesis [21]. For example, IFITM1, IFITM2 and IFITM3 inhibit HIV-1 replication partially through interfering with virus entry [15].…”