Editorial
VIRAL IMMUNOLOGY Volume 28, Number 3, 2015 ª Mary Ann Liebert, Inc. P. 133 DOI: 10.1089/vim.2015.1504
Viral Immunology 2015.28:133-133. Downloaded from online.liebertpub.com by KUNGLIGA TEKNISKA HOGSKOLAN on 08/15/15. For personal use only.
Development of New Assays for Epstein–Barr and Porcine Epidemic Diarrhea Viruses David L. Woodland
T
he development of diagnostic assays for viruses or viral signatures of infection is a staple of the viral immunologist. Several categories of tests can be employed that (i) directly assay the presence of viral particles, virus antigen, or viral nucleic acids; (ii) indirectly assay the presence of replicating virus in cultured samples; or (iii) serologically assay the impact of a current or past viral infection. The use of each type of assay depends on the circumstances and goals of the analysis and the sensitivity, specificity, and accuracy required. In the current issue of Viral Immunology, two new viral assays are described and analyzed in detail. Chen et al. have developed a fluorescence immunoassay designed to detect Epstein–Barr virus (EBV) reactivation (the switch from latency to lytic replication) in infected patients. The assay detects immunoglobulin A (IgA) antibodies in human serum specific for the EBV transactivator protein (ZEBRA), an immediate-early protein involved in the reactivation process. A comparison of the new assay with a commercial enzymelinked immunosorbent assay (ELISA) kit on a large number of samples revealed good agreement between the assays, and further demonstrated that the new assay was more sensitive and had potential value in automation and high-throughput screening. In a second article, Wang et al. describe the development of a new assay for porcine epidemic diarrhea virus (PEDV), which causes acute diarrhea and dehydration in pigs. The authors produced monoclonal antibodies against PEDV and used them to establish a sensitive and specific ELISA assay suitable for screening large numbers of specimens. The new assay will be an important tool for the diagnosis and epidemiological analysis of PEDV infections. Two articles in this issue of Viral Immunology address the control of dengue virus (DENV), a single positive-stranded RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. DENV infection is a major infectious disease challenge causing febrile disease, and it infects 50–100 million people annually. Farias et al. have investigated the use of chloroquine as an antiviral drug against DENV in monkeys. The authors show that chloroquine reduces the replication of DENV in Aotus monkeys and also reduces the levels of tumor necrosis factor alpha and interferon gamma in the serum. They suggest that chloroquine should be further tested in patients with dengue disease to
confirm the drug’s clinical effect and to assess the side effects. In a separate study, Diwaker et al. have investigated the role of lipid rafts in DENV immunopathogenesis. They show that host protein disulfide isomerase (PDI) interacts with viral NS1 protein and co-localizes with lipid rafts on the cell surface. The authors argue that disruption of this key interaction between PDI and NS1 could be an important therapeutic strategy to block DENV infection. Other articles in this issue address various aspects of the immune response to viral infection. Spits et al. note that a recently conducted multicenter randomized trial demonstrated that temporary early combination antiretroviral therapy lowered the viral setpoint and deferred the need for reinitiation of therapy during chronic human immunodeficiency virus (HIV) infection. To determine whether the beneficial effect of early treatment was caused by preservation of immunological responses, the authors analyzed various immunological parameters in treated and untreated individuals. The only clear difference identified was an increase in the quality of the cytolytic CD4 T-cell response. It remains to be determined whether this subtle immunological difference was the cause or a result of the lower viral setpoint in patients who received early treatment. In a separate report, Rogalska–Plon´ska et al. report on the influence of HIV and hepatitis C virus (HCV) on the development of cryoglobulinemia, a syndrome characterized by systemic inflammation of small- and medium-sized vessels and accompanied by multiorgan damage. Their data indicate that HCV monoinfection and HCV/HIV coinfection are potent stimulators of cryoglobulinemia. They also conclude that effective antiretroviral therapy protects against cryoglobulinemia development in HIV monoinfected patients. Influenza A virus hemagglutinin-specific IgA is thought to play an important role in the prevention of influenza virus infection, although this has been difficult to demonstrate through topical administration of the antibody. In this regard, Shoji et al. established a recombinant hybrid IgA comprised of the variable regions of an HAspecific mouse IgG and the heavy chain constant region of a mouse IgA. This new reagent will promote further study into the role of IgA at the mucosal surface. I would like to thank all of the authors and reviewers that contributed to this excellent edition of Viral Immunology.
Keystone Symposia on Molecular and Cellular Biology, Silverthorne, Colorado.
133
VIRAL IMMUNOLOGY Volume 28, Number 3, 2015 ª Mary Ann Liebert, Inc. P. 133 DOI: 10.1089/vim.2015.1504
Viral Immunology 2015.28:133-133. Downloaded from online.liebertpub.com by KUNGLIGA TEKNISKA HOGSKOLAN on 08/15/15. For personal use only.
Development of New Assays for Epstein–Barr and Porcine Epidemic Diarrhea Viruses David L. Woodland
T
he development of diagnostic assays for viruses or viral signatures of infection is a staple of the viral immunologist. Several categories of tests can be employed that (i) directly assay the presence of viral particles, virus antigen, or viral nucleic acids; (ii) indirectly assay the presence of replicating virus in cultured samples; or (iii) serologically assay the impact of a current or past viral infection. The use of each type of assay depends on the circumstances and goals of the analysis and the sensitivity, specificity, and accuracy required. In the current issue of Viral Immunology, two new viral assays are described and analyzed in detail. Chen et al. have developed a fluorescence immunoassay designed to detect Epstein–Barr virus (EBV) reactivation (the switch from latency to lytic replication) in infected patients. The assay detects immunoglobulin A (IgA) antibodies in human serum specific for the EBV transactivator protein (ZEBRA), an immediate-early protein involved in the reactivation process. A comparison of the new assay with a commercial enzymelinked immunosorbent assay (ELISA) kit on a large number of samples revealed good agreement between the assays, and further demonstrated that the new assay was more sensitive and had potential value in automation and high-throughput screening. In a second article, Wang et al. describe the development of a new assay for porcine epidemic diarrhea virus (PEDV), which causes acute diarrhea and dehydration in pigs. The authors produced monoclonal antibodies against PEDV and used them to establish a sensitive and specific ELISA assay suitable for screening large numbers of specimens. The new assay will be an important tool for the diagnosis and epidemiological analysis of PEDV infections. Two articles in this issue of Viral Immunology address the control of dengue virus (DENV), a single positive-stranded RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. DENV infection is a major infectious disease challenge causing febrile disease, and it infects 50–100 million people annually. Farias et al. have investigated the use of chloroquine as an antiviral drug against DENV in monkeys. The authors show that chloroquine reduces the replication of DENV in Aotus monkeys and also reduces the levels of tumor necrosis factor alpha and interferon gamma in the serum. They suggest that chloroquine should be further tested in patients with dengue disease to
confirm the drug’s clinical effect and to assess the side effects. In a separate study, Diwaker et al. have investigated the role of lipid rafts in DENV immunopathogenesis. They show that host protein disulfide isomerase (PDI) interacts with viral NS1 protein and co-localizes with lipid rafts on the cell surface. The authors argue that disruption of this key interaction between PDI and NS1 could be an important therapeutic strategy to block DENV infection. Other articles in this issue address various aspects of the immune response to viral infection. Spits et al. note that a recently conducted multicenter randomized trial demonstrated that temporary early combination antiretroviral therapy lowered the viral setpoint and deferred the need for reinitiation of therapy during chronic human immunodeficiency virus (HIV) infection. To determine whether the beneficial effect of early treatment was caused by preservation of immunological responses, the authors analyzed various immunological parameters in treated and untreated individuals. The only clear difference identified was an increase in the quality of the cytolytic CD4 T-cell response. It remains to be determined whether this subtle immunological difference was the cause or a result of the lower viral setpoint in patients who received early treatment. In a separate report, Rogalska–Plon´ska et al. report on the influence of HIV and hepatitis C virus (HCV) on the development of cryoglobulinemia, a syndrome characterized by systemic inflammation of small- and medium-sized vessels and accompanied by multiorgan damage. Their data indicate that HCV monoinfection and HCV/HIV coinfection are potent stimulators of cryoglobulinemia. They also conclude that effective antiretroviral therapy protects against cryoglobulinemia development in HIV monoinfected patients. Influenza A virus hemagglutinin-specific IgA is thought to play an important role in the prevention of influenza virus infection, although this has been difficult to demonstrate through topical administration of the antibody. In this regard, Shoji et al. established a recombinant hybrid IgA comprised of the variable regions of an HAspecific mouse IgG and the heavy chain constant region of a mouse IgA. This new reagent will promote further study into the role of IgA at the mucosal surface. I would like to thank all of the authors and reviewers that contributed to this excellent edition of Viral Immunology.
Keystone Symposia on Molecular and Cellular Biology, Silverthorne, Colorado.
133
