Acute Infection of Viral Pathogens and Their Innate Immune Escape

Abstract

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.

Keywords: acute infection; innate immune escape; innate immunity; non-structural protein; viral pathogens.

FIGURE 1

General overview of intracellular innate immune signaling and some representative viral immune escape mechanisms. Sensing virus by PRRs initiates innate immune signaling through the hierarchical activation of PRRs family-specific adaptor proteins (TRIF, MAVS, STING, MYD88, and so forth) to activate transcriptional factors, such as IRF3/5/7, NF-kB, and others. Activated transcriptional factors translocate into nucleus and induce robust expression of IFNs. Secreted IFNs bind to their respective receptors and activate JAK-STAT signaling and form a transcriptional factor called ISGF3. ISGF3, then, translocates into nucleus to induce expression of numerous antiviral effectors (ISGs) to impede viral infection. Although antiviral innate immunity consists of well-equipped arsenals to impede viral infection and invasion, viruses circumvent or escape from these antiviral arsenals to establish successful infection through several mechanisms. Of these escape mechanisms, viral components inhibit innate immune signaling by diversified tactics, such as interacting directly or indirectly with crucial innate elements, targeting and cleaving adaptor proteins involved in innate immune signaling or interference of IFN signaling, degradation of JAK/STAT components, and so forth. Some representative viral immune escape tactics are shown in the Figure 1.