Long noncoding RNAs (lncRNAs) are single-stranded RNA molecules longer than 200 nt that regulate many cellular processes. MicroRNA 155 host gene (MIR155HG) encodes the microRNA (miR)-155 that regulates various signalling pathways of innate and adaptive immune responses against viral infections. MIR155HG also encodes a lncRNA that we call lncRNA-155. Here, we observed that expression of lncRNA-155 was markedly upregulated during influenza A virus (IAV) infection both in vitro (several cell lines) and in vivo (mouse model). Interestingly, robust expression of lncRNA-155 was also induced by infections with several other viruses. Disruption of lncRNA-155 expression in A549 cells diminished the antiviral innate immunity against IAV. Furthermore, knockout of lncRNA-155 in mice significantly increased IAV replication and virulence in the animals. In contrast, overexpression of lncRNA-155 in human cells suppressed IAV replication, suggesting that lncRNA-155 is involved in host antiviral innate immunity induced by IAV infection. Moreover, we found that lncRNA-155 had a profound effect on expression of protein tyrosine phosphatase 1B (PTP1B) during the infection with IAV. Inhibition of PTP1B by lncRNA-155 resulted in higher production of interferon-beta (IFN-β) and several critical interferon-stimulated genes (ISGs). Together, these observations reveal that MIR155HG derived lncRNA-155 can be induced by IAV, which modulates host innate immunity during the virus infection via regulation of PTP1B-mediated interferon response. KEYWORDS influenza A virus, innate immunity, lncRNA, miR-155, MIR155HG, PTP1B List of Abbreviations: 293T, HEK293T/human embryonic kidney cells; A549, human lung epithelial cells; bic, B-cell Integration Cluster; CA/04, A/California/04/2009; DMEM, Dulbecco's modified Eagle's medium; dpi, days post infection; EV, empty vector; FBS, fetal bovine serum; HA, haemagglutination assay; h-lncRNA-155, human lncRNA-155; hpi, hours post infection; IFN, interferon; IFN-β, interferon-beta; IRF3, interferon regulatory factor 3; IRF7, interferon regulatory factor 7; ISGs, interferon-stimulated genes; KO, bic/miR-155 −/− knock out mice; LLC, mouse Lewis lung carcinoma cells; lncRNAs, long noncoding RNAs; NIH/3T3, mouse embryonic fibroblasts; MDA5, antimelanoma differentiation-associated gene 5; MDCK, Madin-Darby canine kidney cells; miR, microRNA; MIR155HG, miR-155 host gene; m-lncRNA-155, bic/mouse lncRNA-155; NP, IAV nucleoprotein; nt, nucleotide; NRAV, negative regulator of antiviral response;PFA, plaque formation assay; PR8, A/Puerto Rico/8/1934; pre-miR-155, precursor miRNA; pri-miRNA, primary-miRNA; PRRs, pattern recognition receptors; PTP1B, tyrosine-protein phosphatase nonreceptor type 1; RAW 264.7, mouse Abelson murine leukaemia virus transformed macrophages; SeV, Sendai virus; SHIP1, Src homology 2-containing inositol phosphatase 1;sh-luc, Sh-luciferase; shRNAs, short hairpin RNAs; siRNA, small interfering RNA; SOCS1, suppressor of cytokine signalling 1; SPF, specific pathogen free; STAT1, signal transducer a...

Viral infections can cause rampant disease in human beings, ranging from mild to acute, that can often be fatal unless resolved. An acute viral infection is characterized by sudden or rapid onset of disease, which can be resolved quickly by robust innate immune responses exerted by the host or, instead, may kill the host. Immediately after viral infection, elements of innate immunity, such as physical barriers, various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, provide the first line of defense for viral clearance. Innate immunity not only plays a critical role in rapid viral clearance but can also lead to disease progression through immune-mediated host tissue injury. Although elements of antiviral innate immunity are armed to counter the viral invasion, viruses have evolved various strategies to escape host immune surveillance to establish successful infections. Understanding complex mechanisms underlying the interaction between viruses and host’s innate immune system would help develop rational treatment strategies for acute viral infectious diseases. In this review, we discuss the pathogenesis of acute infections caused by viral pathogens and highlight broad immune escape strategies exhibited by viruses.

Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular signaling. The viral infection and multiplication process involves complex intracellular molecular interactions between viral components and the host factors. Various types of host cells are also involved to modulate immune factors in delicate and dynamic equilibrium to maintain a balanced immune ecosystem in an infected host tissue. Antiviral host arsenals are equipped to combat or eliminate viral invasion. However, viruses have evolved with strategies to counter against antiviral immunity or hijack cellular machinery to survive inside host tissue for their multiplication. However, host immune systems have also evolved to neutralize the infection; which, in turn, either clears the virus from the infected host or causes immune-mediated host tissue injury. A complex relationship between viral pathogenesis and host antiviral defense could define the immune ecosystem of virus-infected host tissues. Understanding of the molecular mechanism underlying this ecosystem would uncover strategies to modulate host immune function for antiviral therapeutics. This review presents past and present updates of immune-ecological components of virus infected host tissue and explains how viruses subvert the host immune surveillances.