Boosting Host Immunity with Interferon

T ype I interferons (IFNs) are proteins that play a central role in the innate immune response to viral infections. They primarily act by interfering with viral replication within host cells and increasing the ability of uninfected cells to resist new infection by virus. They are also involved in several other functions, including the activation of natural killer (NK) cells and macrophages. The capacity of IFNs to induce an antiviral state has led to their consideration as prophylactic agents to control or attenuate viral infections. Indeed, human IFN-γ administered by oral or intranasal pathways has been demonstrated to elicit considerable antiviral activity against seasonal influenza virus. Two articles in the current issue of Viral Immunology further address this issue. Xu and associates have examined the prophylactic properties of human omega interferon (IFN-ω) which, like IFN-α, is secreted from leukocytes in response to viral infection and has antiviral and immunomodulatory activities. Using a guinea pig model, they show that daily intranasal treatment with human IFN-ω was able to decrease the lung viral load of a pandemic influenza A virus strain (A/California/04/2009) by 1000-fold. The results offer strong support for the application of human IFN-ω pretreatment to human influenza control. Audigé and colleagues have evaluated the effect of IFN-α on in vivo viral replication in mouse models of chronic lymphocytic choriomeningitis virus (LCMV) and acute Friend retrovirus (FV) infection. Exogenous IFN-α inhibited FV replication, but had no effect on LCMV replication.

While IFNs are an important component of the innate immune response to infection, there are also several other contributors to the response, such as NK cells. In this regard, Johansson and colleagues have investigated the role of antibody-dependent cellular cytotoxicity (ADCC) mediated by antiviral antibodies binding to the FcγRIIIa receptor (CD16) on NK cells. Analysis of antibodies in plasma from human immunodeficiency virus-1 (HIV-1)-infected patients and healthy donors revealed that they were largely directed at the HIV-1 envelope protein. Importantly, NK cell ADCC activity was not compromised in HIV-infected patients.

Several articles in the current issue focus on the adaptive immune response to viral infections. It has been previously established that vaccinia virus (VACV) exhibits a strong tropism for ovarian tissue and can cause ovary pathology and sterility. Zhao and colleagues examined several potential mechanisms for the preferential replication of VACV in the ovaries and ultimately concluded that it is independent of immune regulation through IL-10 and TGF-β. Umlauf and colleagues also investigated the immune response to VACV in individuals who had been vaccinated with one dose of Dryvax^®. The authors identified several correlations between inflammatory cytokine levels, neutralizing antibody titers, and secreted IL-2. Interestingly, vaccine-induced inflammatory responses were not correlated with neutralizing antibody titers. This suggests that further attenuation of the vaccine may decrease adverse events without sacrificing immunogenicity and population seropositivity. The adaptive immune response to HIV-1 was investigated by Prakash and associates. They report the capacity of plasma from HIV-1-infected children to efficiently neutralize primary isolates of the virus.

Finally, three papers address questions related to immunogenetics and diagnostics. Liu and colleagues describe a genome-wide association study of the clinical outcomes of hepatitis B virus (HBV) infection. They show that a section of the glutamate receptor, the ionotropic N-methyl-D-aspartate 2A gene, was replicated and had significant associations with disease progression in HBV-infected individuals. In another study, Wang and co-workers demonstrate that the human leukocyte antigen class I Cw 1502 and class II DR 0301 genotypes are associated with resistance to severe acute respiratory syndrome (SARS) virus infection. On the diagnostics front, Zhang and colleagues have developed a sensitive assay for the detection of H5N1 and H9N2 avian influenza. The authors note that it is a powerful method for detecting many pathogens or many types of a pathogen simultaneously.

All in all, this is a very strong issue of Viral Immunology.