EDITORIAL
crossm Classic Spotlight, 1971 to 1973: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors
J
ournal of Virology (JVI) marks its 50th year of publishing in 2017. To highlight particularly noteworthy JVI articles over the years, 2017 issues are featuring Classic Spotlights selected from the archives by the editors. These Classic Spotlights are appearing chronologically, and in this issue, we have selected articles from 1971 to 1973.
Mechanism of Synthesis of Vaccinia Virus Double-Stranded RNA In Vivo and In Vitro Colby et al. (C. Colby, C. Jurale, and J. R. Kates, J Virol 7:71–76, 1971, http:// jvi.asm.org/content/7/1/71.abstract) reported that synthesis of vaccinia virus (VACV) double-stranded RNA (dsRNA) in infected HeLa cells is sensitive to actinomycin D, suggesting that a DNA-dependent reaction is involved. Furthermore, at least 70% of the dsRNA made in vivo was in RNase-resistant form. It was previously shown that purified VACV dsRNA is a very potent inducer of interferon in chick cells. Later studies revealed dsRNA as a pathogen-associated molecular pattern (PAMP) sensed by the innate immune system. Convergent transcription of VACV late genes results in dsRNA as a by-product, and dsRNA is recognized by host cells to trigger PKR activation and cytokine gene transcription. Following these studies, Myskiw et al. (C. Myskiw, J. Arsenio, R. van Bruggen, Y. Deschambault, and J. Cao, J Virol 83:6757– 6768, 2009, https://doi.org/10.1128/JVI.02570-08) demonstrated that the VACV E3 protein can suppress PKR activation by antagonizing the induction of multiple cytokines through several pathways. Thus, the findings of Colby et al. contributed to uncovering host defense and viral counter-defense pathways in VACV infection.
Citation American Society for Microbiology. 2017. Classic Spotlight, 1971 to 1973: Articles of significant interest selected from the Journal of Virology archives by the editors. J Virol 91:e02206-16. https://doi.org/10.1128/ JVI.02206-16. Copyright © 2017 American Society for Microbiology. All Rights Reserved.
Simian Virus 40 DNA Synthesis: the Viral Replicon Tegtmeyer (P. Tegtmeyer, J Virol 10:591–598, 1972, http://jvi.asm.org/content/10/4/ 591.abstract) isolated temperature-sensitive (ts) mutants of simian virus 40 (SV40) deficient in an early function required to produce infectious viral DNA. Temperatureshift experiments showed that the ts protein is required to initiate each new round of viral DNA replication but not required to complete a cycle that had already been initiated. The viral DNA initiator protein also was found to be required to establish stable transformation of 3T3 cells. The ts protein in these mutants was later identified as large T antigen, a multifunctional protein, which is the only viral protein required for SV40 DNA replication because all other factors are provided by the host. T antigen initiates DNA replication by binding to the viral origin of replication. In addition, large T antigen is both necessary and sufficient for initiation and maintenance of transformation of rodent cells in tissue culture. Thus, the ts mutants isolated by Tegtmeyer uncovered two of the important functions of SV40 large T antigen.
February 2017 Volume 91 Issue 3 e02206-16
Journal of Virology
jvi.asm.org 1
Editorial
Journal of Virology
DNA Polymerase Associated with Human Hepatitis B Antigen Kaplan et al. (P. M. Kaplan, R. L. Greenman, J. L. Gerin, R. H. Purcell, and W. S. Robinson, J Virol 12:995–1005, 1973, http://jvi.asm.org/content/12/5/995.abstract) detected DNA polymerase activity in preparations of concentrated human hepatitis B antigen prepared by high-speed centrifugation of antigen-positive human plasma. Inhibitor experiments suggested that DNA is the template for the reaction and that the enzyme is associated with hepatitis B virus (HBV) virions. HBV is characterized by its partially double-stranded circular DNA genome. The viral core-associated DNA polymerase was detected by its capacity to repair the gap in the viral plus strand in vitro. It was later shown that this enzyme plays a key role in the replication of HBV. The DNA polymerase assay, developed by Kaplan et al., was widely used for monitoring antiviral treatments for more than 20 years. However, this method is not sufficiently sensitive to monitor viral loads in the sera of patients receiving antiviral treatment. PCR and real-time PCR are now used to quantify HBV DNA in clinical samples.
February 2017 Volume 91 Issue 3 e02206-16
jvi.asm.org 2
crossm Classic Spotlight, 1971 to 1973: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors
J
ournal of Virology (JVI) marks its 50th year of publishing in 2017. To highlight particularly noteworthy JVI articles over the years, 2017 issues are featuring Classic Spotlights selected from the archives by the editors. These Classic Spotlights are appearing chronologically, and in this issue, we have selected articles from 1971 to 1973.
Mechanism of Synthesis of Vaccinia Virus Double-Stranded RNA In Vivo and In Vitro Colby et al. (C. Colby, C. Jurale, and J. R. Kates, J Virol 7:71–76, 1971, http:// jvi.asm.org/content/7/1/71.abstract) reported that synthesis of vaccinia virus (VACV) double-stranded RNA (dsRNA) in infected HeLa cells is sensitive to actinomycin D, suggesting that a DNA-dependent reaction is involved. Furthermore, at least 70% of the dsRNA made in vivo was in RNase-resistant form. It was previously shown that purified VACV dsRNA is a very potent inducer of interferon in chick cells. Later studies revealed dsRNA as a pathogen-associated molecular pattern (PAMP) sensed by the innate immune system. Convergent transcription of VACV late genes results in dsRNA as a by-product, and dsRNA is recognized by host cells to trigger PKR activation and cytokine gene transcription. Following these studies, Myskiw et al. (C. Myskiw, J. Arsenio, R. van Bruggen, Y. Deschambault, and J. Cao, J Virol 83:6757– 6768, 2009, https://doi.org/10.1128/JVI.02570-08) demonstrated that the VACV E3 protein can suppress PKR activation by antagonizing the induction of multiple cytokines through several pathways. Thus, the findings of Colby et al. contributed to uncovering host defense and viral counter-defense pathways in VACV infection.
Citation American Society for Microbiology. 2017. Classic Spotlight, 1971 to 1973: Articles of significant interest selected from the Journal of Virology archives by the editors. J Virol 91:e02206-16. https://doi.org/10.1128/ JVI.02206-16. Copyright © 2017 American Society for Microbiology. All Rights Reserved.
Simian Virus 40 DNA Synthesis: the Viral Replicon Tegtmeyer (P. Tegtmeyer, J Virol 10:591–598, 1972, http://jvi.asm.org/content/10/4/ 591.abstract) isolated temperature-sensitive (ts) mutants of simian virus 40 (SV40) deficient in an early function required to produce infectious viral DNA. Temperatureshift experiments showed that the ts protein is required to initiate each new round of viral DNA replication but not required to complete a cycle that had already been initiated. The viral DNA initiator protein also was found to be required to establish stable transformation of 3T3 cells. The ts protein in these mutants was later identified as large T antigen, a multifunctional protein, which is the only viral protein required for SV40 DNA replication because all other factors are provided by the host. T antigen initiates DNA replication by binding to the viral origin of replication. In addition, large T antigen is both necessary and sufficient for initiation and maintenance of transformation of rodent cells in tissue culture. Thus, the ts mutants isolated by Tegtmeyer uncovered two of the important functions of SV40 large T antigen.
February 2017 Volume 91 Issue 3 e02206-16
Journal of Virology
jvi.asm.org 1
Editorial
Journal of Virology
DNA Polymerase Associated with Human Hepatitis B Antigen Kaplan et al. (P. M. Kaplan, R. L. Greenman, J. L. Gerin, R. H. Purcell, and W. S. Robinson, J Virol 12:995–1005, 1973, http://jvi.asm.org/content/12/5/995.abstract) detected DNA polymerase activity in preparations of concentrated human hepatitis B antigen prepared by high-speed centrifugation of antigen-positive human plasma. Inhibitor experiments suggested that DNA is the template for the reaction and that the enzyme is associated with hepatitis B virus (HBV) virions. HBV is characterized by its partially double-stranded circular DNA genome. The viral core-associated DNA polymerase was detected by its capacity to repair the gap in the viral plus strand in vitro. It was later shown that this enzyme plays a key role in the replication of HBV. The DNA polymerase assay, developed by Kaplan et al., was widely used for monitoring antiviral treatments for more than 20 years. However, this method is not sufficiently sensitive to monitor viral loads in the sera of patients receiving antiviral treatment. PCR and real-time PCR are now used to quantify HBV DNA in clinical samples.
February 2017 Volume 91 Issue 3 e02206-16
jvi.asm.org 2
