Advances in Innate Antiviral Immunity

The development of an effective adaptive immune response to a viral infection depends on the prompt detection of the invading pathogen and the rapid deployment of countermeasures. In this regard, the innate immune system has evolved to specifically delay, or block, early pathogen replication and signal the adaptive immune response to mobilize cellular and molecular effectors with broad antiviral activity. The importance of the innate arm of the immune response is illustrated by the evasive mechanisms adopted by many viruses to interfere with the engagement of the innate immune system. Furthermore, there is considerable interest in the development of drugs and therapeutics that harness the power of the innate immune system to control viral infection. Over the past decade, considerable advances have been made in identifying key molecules, regulatory pathways, and effector mechanisms that characterize the innate response. But there is still much to learn. In this context, several articles in this issue of Viral Immunology outline advances in our understanding of several aspects of innate antiviral immunity.

The issue opens with a review on antiviral drugs against hepatitis C virus (HCV). Afzal et al. point out that HCV is a major health concern worldwide as it is a leading cause of liver-related mortalities and morbidities. Previously, interferon plus ribavirin-based antiviral therapy played an important role in HCV management across the world. However, interferon treatment can result in negative side effects. In this context, the authors review the development of interferon-free anti-HCV therapeutics and their implications for the treatment of HCV in Pakistan. Peripheral blood mononuclear cells (PBMCs) play a critical role in clearing HCV. PBMC defects have been linked with HCV infection; however, the underlying mechanisms remain obscure. In this context, Alhetheel et al. hypothesize that PBMCs of HCV-infected patients are more susceptible to programmed cell death (PCD) and are, therefore, unable to clear HCV. Their data indicate that HCV infection is associated with increased PBMC susceptibility to PCD and decreased production of a number of cytokines, including interleukin (IL)-8, -6, and -10.

Much research in innate immunity has focused on identifying the genes that play critical roles in mediating the response. In this regard, Wujcicka et al. have analyzed single nucleotide polymorphisms to understand the relationship between polymorphisms IL1A, IL1B, and IL6 genes and in the occurrence and development of human cytomegalovirus (HCMV) infection among pregnant women. The authors' data suggest that polymorphisms in these genes are associated with protection against HCMV infection in the studied patient group. Along similar lines, Neco et al. have investigated the association between polymorphisms in the IL17A gene and the development of human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy and tropical spastic paraparesis. Their study found no significant differences in genotypic and allelic frequencies between symptomatic and asymptomatic patients with a positive diagnosis of HTLV-1. Akbal et al. note that toll-like receptors (TLRs), which play a key role in pathogen detection, may be involved in hepatitis B virus (HBV) pathogenesis. However, the association between the levels of TLRs, liver enzymes, HBV DNA, and HBV surface antigen in the serum is unknown. Here the authors report a positive correlation between serum TLR-2, TLR-4, HBV DNA, and alanine aminotransferase levels. These data support the idea that TLRs play an important role in HBV pathogenesis.

The remaining articles in this issue of Viral Immunology address other aspects of the immune response to viral infections. Wong et al. report that a recombination has occurred between canine adenoviruses 1 and 2, which may explain vaccine failures or increased virulence of the virus in the observed canine hepatitis cases. Memon et al. have developed and validated a monoclonal antibody-based antigen capture ELISA for the detection of group A porcine Rotavirus. Finally, Ramamoorthy et al. report that high levels of caffeine consumption is associated with higher CD4 cell counts and lower human immunodeficiency virus (HIV) viral loads, possibly indicating beneficial effects on HIV disease progression.

I would like to thank all of the authors and reviewers for their contributions to this issue of Viral Immunology.