Immunomodulatory Agents

Multiple host factors control the development of an immune response to a viral infection and provide opportunities for therapeutic intervention in the outcome of an infection. The current issue of Viral Immunology features an article that further investigates this concept of manipulating host immune responses to therapeutic advantage. Indoleamine 2,3-dioxygenase (IDO) is an immune modulatory enzyme expressed by antigen presenting cells (APCs) in response to proinflammatory mediators such as interferons and TNF-α. Influenza A virus infection has been shown to induce IDO, which enhances the primary T cell response by increasing Th1 and virus-specific CD8+ T cell responses. However, it was not known whether these changes impacted the memory T cell response to influenza virus challenge. Sage and colleagues have addressed this question by pharmacologically inhibiting IDO activity with 1-methyl-tryptophan (1MT) during the primary response to influenza virus infection in a mouse model. The authors show that 1MT treatment improved several aspects of the memory T cell response to influenza virus challenge, including increased interferon gamma expression by CD4 and CD8 T cells, increased numbers of lung virus-specific CD8 T cells, increased responses to subdominant epitopes, and evidence of accelerated lung tissue repair upon virus challenge. These exciting data suggest that modulation of IDO activity could be exploited in influenza vaccine development to enhance memory T cell responses and reduce disease burden.

Two other reports in this issue also focus on influenza virus infections. Kumar et al. point out that Influenza A virus infection is associated with increased morbidity and mortality in pregnant women. Indeed, women in the second and third trimester of pregnancy are in a high-risk group during seasonal influenza epidemics. Kumar et al. now show that influenza viruses are able to infect and replicate in human placental cells and induce innate signaling molecules, such as type I interferon and pro-inflammatory cytokines. These data suggest that the influenza virus may potentially replicate at the maternal–fetal interface with implications for adverse immediate and late outcomes during pregnancy. Huang et al. have studied the seroprevalence against influenza H3N2 and pandemic H1N1 and infection in Guangdong, China, following the influenza epidemic in 2012. The authors note that pandemic H1N1 influenza was not present in Guangdong in 2012 and that the seroprevalence of pandemic H1N1 remained below 50% in all age groups following the 2012 influenza season. They conclude that vaccination against pandemic H1N1 antigens should be conducted before the next influenza season.

The remaining three articles in this issue of Viral Immunology address three different viruses that are all associated with potentially severe disease outcomes. First, Teng et al. have made progress in developing a safe vaccine against rotavirus (RV) infection. Although two oral live RV vaccines are currently available, they are both associated with risks for adverse effects. To address this problem, the authors created VP6 chimeric recombinant vaccines and analyzed their immunogenicity in a guinea pig model. They anticipate that this VP6-based epitope presenting system will contribute to the development of novel RV vaccines and vaccine vectors that may be safer. Second, Wang and colleagues have analyzed the relationships between iNKT and Coxsackievirus B3-induced myocarditis in BALB/c mice. The authors show that the ratio of iNKT and CD3+ cell numbers in the spleen correlated negatively with the degree of inflammation in the heart. These data suggest that iNKT cell numbers might be used as a parameter for the diagnosis of myocarditis in clinical practice. Third, Imran et al. have investigated the relationship between single nucleotide polymorphisms in the host 2′–5′oligoadenylate synthetase (OAS) gene and the efficacy of interferon based therapies against Hepatitis C Virus. Their data indicate that polymorphisms in the exon 7 splice acceptor site of the OAS1 gene were significantly associated with responsiveness to interferon therapy.

Finally, I would like to thank all of the authors for their excellent contributions to the journal.