crossm Classic Spotlight, 1976 and 1977: 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 1976 and 1977.
Naturally Occurring Murine Leukemia Viruses in Wild Mice: Characterization of a New “Amphotropic” Class Hartley and Rowe (J. W. Hartley and W. P. Rowe, J Virol 19:19 –25, 1976, http:// jvi.asm.org/content/19/1/19.abstract) described a new class of murine leukemia viruses (MLVs) isolated from wild Mus musculus trapped in California, which they designated “amphotropic.” These viruses replicate in mouse, rabbit, mink, human, guinea pig, and rat cells but not in hamster, quail, or duck cells. The amphotropic viruses display N-tropism for mouse cells and do not trigger the XC cell response. Receptor use and envelope (env) sequence variations deﬁne three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic (E-, P-, and X-MLVs). It was later shown that California wild mice carry a subtype of E-MLVs, termed Cas laboratory mice amphotropic MLV (A-MLV), which uses the phosphate transporter PiT-2 for entry. Bamunusinghe et al. (D. Bamunusinghe et al., J Virol 90:4186 – 4198, 2016, https:// doi.org/10.1128/JVI.03186-15) recently analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice. They found a new MLV host range subgroup isolated from mice from Thailand and California. However, with the exception of the env gene, the Cas genome closely resembles that of A-MLV, a mouse gammaretrovirus with a host range found only in California wild mice, as originally described by Hartley and Rowe.
Citation American Society for Microbiology. 2017. Classic Spotlight, 1976 and 1977: Articles of signiﬁcant interest selected from the Journal of Virology archives by the editors. J Virol 91:e02374-16. https://doi.org/10.1128/ JVI.02374-16. Copyright © 2017 American Society for Microbiology. All Rights Reserved.
Adenovirus Transcription. IV. Synthesis of Viral-Speciﬁc RNA in Human Cells Infected with Temperature-Sensitive Mutants of Adenovirus 5 Berget et al. (S. M. Berget, S. J. Flint, J. F. Williams, and P. A. Sharp, J Virol 19:879 – 889, 1976, http://jvi.asm.org/content/19/3/879.abstract) analyzed temperature-sensitive mutants of adenovirus 5 (Ad5) for alterations in late RNA synthesis using single-stranded DNA probes produced by strand separation of fragments generated by cleavage of viral DNA by restriction endonucleases. Two mutants defective in DNA synthesis failed to make wild-type levels of late RNA at the nonpermissive temperature, and interestingly, nuclear RNA resembled early cytoplasmic RNA rather than late nuclear RNA. It was previously reported that Ad nuclear RNA contains sequences not transported to the cytoplasm during the early and late periods of infection. Thus, the processing of nuclear RNA had been suggested as a possible mechanism to regulate viral transcription in Ad-infected cells. In a now classic paper, Berget et al. (S. M. Berget, C. Moore, and P. A. Sharp, Proc Natl Acad Sci U S A 74:3171–3175, 1977, https://doi.org/ 10.1073/pnas.74.8.3171) reported that the 5= end of the Ad2 late mRNA for the hexon protein was not encoded in the region of Ad2 DNA that encodes most of hexon mRNA. When hybrids of hexon mRNA and single-stranded restriction endonuclease March 2017 Volume 91 Issue 5 e02374-16
Journal of Virology
Journal of Virology
fragments of viral DNA were visualized by electron microscopy, branched forms were observed in which ⬃200 nucleotides of RNA from the 5= terminus were not hydrogen bonded to the DNA. In the same year, it was reported by Chow et al. [L. T. Chow, R. E. Gelinas, T. R. Broker, and R. J. Roberts, Cell 12:1– 8, 1977, https://doi.org/ 10.1016/0092-8674(77)90180-5] that the 5= terminal sequences of several Ad2 mRNAs isolated late in infection were complementary to sequences within the Ad2 genome that are remote from the DNA coding sequence of each mRNA. This complementation was also shown by electron microscopic visualization of DNA-RNA hybrids or “R loops.” In the Discussion of Berget et al. (S. M. Berget, C. Moore, and P. S. Sharp, Proc Natl Acad Sci U S A 74:3171–3175, 1977, https://doi.org/10.1073/pnas.74.8.3171), it was posited that a model for the synthesis of the mature hexon mRNA would be the intramolecular joining of short RNA segments to the body of the hexon mRNA during the processing of a nuclear precursor to generate the mature mRNA. This was the discovery of pre-mRNA splicing. Tunicamycin Inhibits Glycosylation and Multiplication of Sindbis and Vesicular Stomatitis Viruses Leavitt et al. (R. Leavitt, S. Schlesinger, and S. Kornfeld, J Virol 21:375–385, 1977, http://jvi.asm.org/content/21/1/375.abstract) reported that tunicamycin (TM) inhibits the growth of Sindbis virus and vesicular stomatitis virus in BHK cells. TM is an antibiotic that inhibits the formation of N-acetylglucosamine–lipid intermediates, thus preventing the glycosylation of newly synthesized glycoproteins. TM did not affect the replication of the nonenveloped encephalomyocarditis virus, demonstrating that TM is not a general inhibitor of protein synthesis. TM speciﬁcally inhibits the glycosylation of viral glycoproteins, and it was proposed that glycosylation is essential for the normal assembly of enveloped viral particles. Subsequent studies have shown that TM affects the infectivity of several enveloped viruses by preventing N-linked glycosylation. Concordantly, TM also induces the unfolded protein response. Stimulation of Cellular Thymidine Kinases by Human Cytomegalovirus Estes and Huang (J. E. Estes and E.-S. Huang, J Virol 24:13–21, 1977, http://jvi.asm .org/content/24/1/13.abstract) showed that human cytomegalovirus (HCMV) strain AD169 stimulates cellular thymidine kinase (TK) during infection. A hallmark of HCMV infection of quiescent cells is the upregulation of many host cell proteins, including DNA replication enzymes, which are required for viral gene expression and viral DNA replication. HCMV induces quiescent cells to enter the cell cycle and then arrests cells in late G1, before they enter the S phase, which is a favorable state for viral replication. In later studies, Kalejta and Shenk (R. F. Kalejta and T. Shenk, J Virol 77:3451–3459, 2003, http://jvi.asm.org/content/77/6/3451.abstract) reported that HCMV pp71, the protein product of the UL82 gene, can accelerate the movement of cells through the G1 phase of the cell cycle. HCMV pp71 also induces DNA synthesis in quiescent cells and thus may stimulate the infectious cycle.
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