Cutting-Edge Articles on the Host Response to Viral Infections

I am proud to present a superb issue of Viral Immunology, which features several highly significant and cutting-edge articles addressing different aspects of the host response to viral infections. The issue opens with a review article from Low and colleagues that discusses the question of whether male vaccination can reduce human papillomavirus (HPV)-related disease in the United States. HPV can cause cervical cancer in women, as well as a number of other diseases in both men and women. Although both genders play a role in the transmission of the viruses, current vaccination efforts in the U.S. focus on women. In this regard, the review broaches several critical issues related to male vaccination. I think that you will find the review informative and interesting.

Three other articles in this issue also address vaccine development. Choi and colleagues have investigated a novel approach to developing a respiratory syncytial virus (RSV) vaccine. RSV is a primary cause of severe lower respiratory tract disease in infants, young children, and the elderly worldwide. The virus' G protein mimics a key host chemokine, CX3C, and thereby modifies the host immune response by affecting pulmonary leukocyte chemotaxis. The authors show that vaccines that induce antibodies that block RSV G protein binding to CX3CR1 cross-neutralize both A and B strains of RSV. This approach may provide a disease intervention strategy for the control of RSV.

Another clinically-significant respiratory infection is influenza. Current influenza virus vaccines have limited efficacy, although new vaccines are under development. Tregnaghi and colleagues report on the immunogenicity, safety, and tolerability of two trivalent subunit inactivated influenza vaccines during a Phase III trial. Both vaccines were safe and well-tolerated, and elicited robust immunogenic responses in all age groups, suggesting that they are appropriate for annual vaccination campaigns. Influenza is also an important problem for the poultry business. Mallick and colleagues examined the protective efficacy of a virosome-based avian influenza virus vaccine against a homologous influenza virus challenge in chickens. The authors show that CpG-adjuvants significantly reduced influenza virus shedding, and elicit virus-specific protective antibody responses in vaccinated birds.

Persistent viral infections are typically characterized by impaired T-cell responses, and several immune-regulatory pathways, such as IL-10 and TGF-β, have been shown to be involved in the induction of T-cell exhaustion and viral persistence. Boettler and associates investigated whether TGF-β signaling is involved in maintaining T-cell exhaustion, and whether blocking TGF-β signaling could improve control of viral replication. Using a mouse model of persistent lymphocytic choriomeningitis virus infection, the authors show that blockage in vivo of the TGF-β receptor failed to enhance the antiviral T-cell response, and did not mediate a therapeutically-relevant reduction of viral titers. The data indicate that TGF-β receptor blockade may not be a viable strategy to tackle persistent viruses.

Another clinically-significant virus that establishes persistent infection is herpes simplex virus-1 (HSV-1). Alami and co-workers recently discovered that the HSV-1 latency-associated transcript (LAT) results in exhaustion of virus-specific CD8⁺ T cells in latently-infected trigeminal ganglia. These authors now provide evidence for an immune-evasion mechanism in which HSV-1 LAT interferes with dendritic cell phenotypic and functional maturation. The effect of LAT on trigeminal ganglia-resident dendritic cells may contribute to the reduced function of HSV-specific CD8⁺ T cells.

The final article in this issue addresses the potential role of enterovirus infections in the etiology of type 1 diabetes. It has been known for some time that type 1 diabetes is strongly associated with certain human leukocyte antigen (HLA) class II haplotypes. Witsø and colleagues examined whether HLA genotypes conferring varying degrees of risk for diabetes were associated with enterovirus gut infections. The authors conclude that there is no statistically significant association between HLA genotypes and the occurrence of human enterovirus gut infections.

Taken together, the research presented in this issue of Viral Immunology considerably extends our understanding of the host response to both acute and persistent viral infections, and provides important information necessary for the development of vaccines and therapeutics.