Host-virus interaction and viral evasion

Abstract

With each infectious pandemic or outbreak, the medical community feels the need to revisit basic concepts of immunology to understand and overcome the difficult times brought about by these infections. Regarding viruses, they have historically been responsible for many deaths, and such a peculiarity occurs because they are known to be obligate intracellular parasites that depend upon the host's cell machinery for their replication. Successful infection with the production of essential viral components requires constant viral evolution as a strategy to manipulate the cellular environment, including host internal factors, the host's nonspecific and adaptive immune responses to viruses, the metabolic and energetic state of the infected cell, and changes in the intracellular redox environment during the viral infection cycle. Based on this knowledge, it is fundamental to develop new therapeutic strategies for controlling viral dissemination, by means of antiviral therapies, vaccines, or antioxidants, or by targeting the inhibition or activation of cell signaling pathways or metabolic pathways that are altered during infection. The rapid recovery of altered cellular homeostasis during viral infection is still a major challenge. Here, we review the strategies by which viruses evade the host's immune response and potential tools used to develop more specific antiviral therapies to cure, control, or prevent viral diseases.

Keywords: cytokines; immunity; immunology; interleukins; oxidative stress; viruses.

Figure 1

Representation of TLR activation by their respective PAMPs and the subsequent immune response. The rectangle in the upper left corner shows the PAMPs recognized by the intracellular TLRs 3, 7, 8, and 9. AP‐1, activator protein 1; dsRNA, double‐stranded RNA; IFN, interferon; IRF, interferon regulatory factor; MyD88, myeloid differentiation primary response 88 protein; NF‐κB, nuclear factor kappa B; RIG, retinoic acid‐inducible gene; ssRNA, single‐stranded RNA; TLR, Toll‐like receptor

Figure 2

Mechanisms of nonspecific immune response mediated by cells. (a) M1‐polarized macrophage subtype and M2‐polarized macrophage subtype stimulation leading to distinct responses related to viral persistence and progression. (b) Dendritic cell response after activation of TLRs. (c) Deregulation of the interaction between NK cells and dendritic cells leading to viral disease progression. Arg1, arginase 1; DENV, dengue virus; H1N1, swine influenza virus A; H5N1, avian influenza virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HSV, herpes simplex virus type 1; IFN, Interferon; IL, interleukin; JEV, japanese encephalitis virus; LPS, lipopolysaccharide; NK, natural killer cells; NO; nitric oxide; NOS2, nitric oxide synthase 2; VSV, Indiana vesiculovirus; VV, vaccinia virus

Figure 3

Mechanisms of an acquired immune response against viruses. (a) Antibodies produced by B cells neutralize viral antigens. (b) The HIV‐1 Tat and Nef proteins interfere with MHC class II molecules, and as a consequence disrupt the generation of virus‐specific CD4+ T cells essential to an effective antiviral immune response. (c) Specific cytokines stimulate the CD8+ T cell‐mediated response. HCV chronic infection causes sustained stimulation of TCR and positive regulation of inhibitory receptors that lead to the depletion of CD8+ T cell effectors. APC, antigen‐presenting cell; HCV, hepatitis C virus; Nef, negative regulatory factor; Tat, trans‐activator of transcription

Figure 4

Mechanisms underlying strategies of viral evasion from the immune response. The rectangle in the upper left corner shows the receptors and their ligands involved in various strategies of viral escape. Numbers show: (1) Latent HIV‐1 infection; (2) gp120 epitope mutation; (3) Bcl homologue production; (4) gp120 association with CXCR4 or CCR5; (5) ILs binding ILR; (6) Inhibition of proteasomal degradation; (7) TAP‐mediated transport blockade (8,9) Inhibition of presentation by MHC class I and its analogues; (10) Inhibition of apoptosis by Bcl homologues. Bcl‐2, B‐cell lymphoma 2; CCR5, C‐C chemokine receptor type 5; CXCR4, C‐X‐C chemokine receptor type 4; ILR, interleukin receptor