crossm Classic Spotlight, 1982 and 1983: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors


ournal of Virology (JVI) marks its 50th year of publishing in 2017. To highlight particularly noteworthy JVI articles from 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 1982 and 1983.

Evidence for Intramolecular Self-Cleavage of Picornaviral Replicase Precursors Palmenberg and Rueckert (A. C. Palmenberg and R. R. Rueckert, J Virol 41:244 –249, 1982, http://jvi.asm.org/content/41/1/244.abstract) analyzed cleavage of protein C of encephalomyocarditis virus. Protein C is a precursor protein that when cleaved produces a virus-coded protease termed p22. Here, the authors showed that protein C is cleaved by two different mechanisms, which were distinguished by their sensitivity to dilution when viral RNA was translated in cell extracts of rabbit reticulocytes. One mechanism was sensitive to dilution, while the other was not, suggesting that both types of cleavage are mediated by viral translation products. The authors proposed that the dilution-sensitive cleavage of protein C is due to a virus-coded protease, probably p22 itself, and that the dilution-independent cleavage is due to intramolecular self-cleavage of protein C. Further evidence for an intramolecular excision of the 3C protease from poliovirus, another picornavirus, was provided by Hanecak et al. (R. Hanecak, B. L. Semler, H. Ariga, C. W. Anderson, and E. Wimmer, Cell 37:1063–1073, 1984, https://doi.org/10.1016/0092-8674(84)90441-0). These data suggest that the autocatalytic excision of protein C from the polyprotein can be either intramolecular or intermolecular.

Citation American Society for Microbiology. 2017. Classic Spotlight, 1982 and 1983: Articles of significant interest selected from the Journal of Virology archives by the editors. J Virol 91:e00083-17. https://doi.org/10.1128/ JVI.00083-17. Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Molecular Cloning and Characterization of Human Papillomavirus DNA Derived from a Laryngeal Papilloma Gissmann et al. (L. Gissmann, V. Diehl, H. J. Schultz-Coulon, and H. zur Hausen, J Virol 44:393– 400, 1982, http://jvi.asm.org/content/44/1/393.abstract) isolated papillomavirus DNA from a laryngeal papilloma and cloned it in phage lambda. The cloned DNA was characterized after cleavage using different restriction enzymes and by hybridization with the DNAs of human papillomavirus 1 (HPV-1), -2, -3, -4, -5, and -8. No homology was seen under stringent hybridization conditions. However, HPV-6 DNA was partially identical to laryngeal papillomavirus DNA as determined by reassociation kinetics. Laryngeal HPV therefore represents a different type of HPV and was designated HPV type 11. It is now recognized that HPV-6 and HPV-11 are common causes of genital warts and respiratory papillomas. The quadrivalent HPV vaccine in use today protects against HPV-6 and HPV-11 as well as the highly oncogenic HPV-16 and HPV-18. Nucleotide Sequence and Organization of the Adeno-associated Virus 2 Genome Adeno-associated viruses (AAV) are helper-dependent members of the parvovirus group that require coinfection with an unrelated helper virus, which is adenovirus for AAV. The replication cycle of AAV involves two phases. Productive replication is April 2017 Volume 91 Issue 8 e00083-17

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dependent on coinfection with adenovirus, whereas AAV latency is established in the absence of a helper virus. Srivastava et al. (A. Srivastava, E. W. Lusby, and K. I. Berns, J Virol, 45:555–564, 1983, http://jvi.asm.org/content/45/2/555.abstract) determined the complete nucleotide sequence of the AAV 2 genome, which is the most highly studied AAV type. The single-stranded genome is 4,675 nucleotides in length and contains inverted terminal repeats of 145 nucleotides. Genome segments were assigned that encode the three major viral capsid proteins and some unidentified nonstructural viral proteins. AAV is now widely used as a gene transfer vector, and while several distinct serotypes of AAV have been identified, serotype 2 is the most commonly used for gene transfer. AAV vectors have a favorable safety profile relative to other vectors, as no AAV serotype has been implicated as a causative agent in human disease. Recent studies have demonstrated that AAV vectors can elicit both a humoral and cellular immune response. However, AAV-induced immune responses are less robust than those triggered by other viral vectors, such as adenovirus, making AAV a preferred vector for in vivo gene transfer (S. Daya and K. I. Berns, Clin Microbiol Rev, 21:583–593, 2008, https://doi.org/10.1128/CMR.00008-08). Characterization of the Herpes Simplex Virion-Associated Factor Responsible for the Induction of ␣ Genes Herpes simplex virus 1 (HSV-1) genes form three groups, ␣, ␤, and ␥, whose expression is tightly regulated such that transcription occurs in a cascade: ␣, then ␤, and finally ␥. An important question that Batterson and Roizman (W. Batterson and B. Roizman, J Virol, 46:371–377, 1983, http://jvi.asm.org/content/46/2/371.abstract) addressed was how the cellular transcription machinery, which transcribes the HSV-1 genome, distinguishes between these classes of viral genes. The authors constructed chimeric genes consisting of a portion of the 5= noncoding leader sequences and the sequences upstream of the transcription initiation site of four ␣ genes encoding ICP0, ICP4, ICP22, and ICP27 fused to the structural sequences of the HSV-1 thymidine kinase (TK) gene, a ␤ gene. Upon transfection of the chimeric genes into TK⫺ cells, the cells were converted to the TK⫹ phenotype. Further, the chimeric genes were induced by infection with homologous TK⫺ virus and the induction of the resident chimeric gene did not require viral protein synthesis. UV light-irradiated virus was just as effective as untreated virus in inducing ␣-TK gene chimeras. The authors concluded that the ␣ gene inducer is a virion component located outside the capsid and that its function might be to stimulate the transcription of the ␣ genes by recognizing regulatory sites on viral DNAs, host cell products, or both. Later studies by several groups, including the Roizman group, identified the HSV-1 tegument protein VP16 as the ␣ trans-inducing protein, which interacts with cellular factors Oct-1 and HCF to target TAATGARAT sequences present in the upstream regions of ␣ gene promoters and not in the promoters of ␤ and ␥ genes.

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Classic Spotlight, 1982 and 1983: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors.

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