crossm Classic Spotlight, 1996 and 1997: 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 1996 and 1997.

Primary Characterization of a Herpesvirus Agent Associated with Kaposi’s Sarcomae Kaposi’s sarcoma (KS) is a neoplasm occurring in both human immunodeficiency virus (HIV)-infected and uninfected persons. Epidemiologic studies suggested that KS has an infectious etiology. Chang et al. [Y. Chang et al., Science 266(5192):1865–1869, 1994, https://doi.org/10.1126/science.7997879] isolated unique DNA sequences from KS tissues obtained from patients with AIDS. The sequences were homologous to, but distinct from, capsid and tegument protein genes of the gammaherpesviruses. Moore et al. (P. S. Moore et al., J Virol 70:549 –558, 1996, http://jvi.asm.org/content/70/1/549 .abstract) characterized this virus using a continuously infected B-lymphocyte cell line derived from an AIDS-related lymphoma and a genomic library made from a KS lesion. The viral genome was present as an episomal genome. A region of 20.7 kb of the genome was sequenced, revealing 17 partial and complete open reading frames; all except one had sequence and positional homology to known gammaherpesvirus genes. Phylogenetic analyses demonstrated that the agent is a gamma-2 herpesvirus (genus Rhadinovirus) and is the first member of this genus known to infect humans. Sera from patients with KS were shown to have specific antibodies against antigens of infected cell lines, and these antibodies were absent in sera from AIDS patients without KS. These studies defined the virus as a new human herpesvirus, Kaposi’s sarcomaassociated herpesvirus (KSHV).

Citation American Society for Microbiology. 2017. Classic Spotlight, 1996 and 1997: Articles of significant interest selected from the Journal of Virology archives by the editors. J Virol 91:e00775-17. https://doi.org/ 10.1128/JVI.00775-17. Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Efficient Long-Term Gene Transfer into Muscle Tissue of Immunocompetent Mice by Adeno-associated Virus Vector Gene transfer into muscle was considered an attractive target for the treatment of several diseases, including Duchene’s muscular dystrophy. However, somatic delivery with several vector systems resulted in transient expression due to silencing of the transgene or to an immune response against the vector-transduced cells. Xiao et al. (X. Xiao, J. Li, and R. J. Samulski, J Virol 70:8098 – 8108, 1996, http://jvi.asm.org/content/ 70/11/8098.abstract) used a recombinant adeno-associated virus (rAAV) vector consisting only of AAV inverted terminal repeats necessary for replication, packaging, and integration and removed all viral coding sequences, which comprise 96% of the genome and without which wild-type helper virus cannot be generated nor can immune responses to residual viral gene expression. In place of the 4.4-kb coding region, the virus can carry and express nonviral genes of up to 5 kb and can infect both dividing and nondividing cells. Importantly, the rAAV genome integrates into the host chromosome with the potential for long-term transduction. Xiao et al. introduced an rAAV vector carrying a lacZ reporter gene into muscle tissue of immunocompetent August 2017 Volume 91 Issue 15 e00775-17

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mice. The lacZ reporter gene was efficiently transduced and expressed with no evidence of a cellular immune response. Gene expression persisted for more than 1.5 years, and the authors found that vector episomes were converted to high-molecularweight genomic DNA. Thus, rAAV vectors can be used for long-term gene transduction into mammalian muscle cells without the need for immune modulation of the organism.

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Construction of Adenovirus Vectors through Cre-lox Recombination Adenoviruses are appealing candidates for gene delivery applications in medicine. The virus infects both resting and dividing cells of many types, and high titer purified virus can be produced. However, the difficulty of making new adenovirus recombinants and the strong immunological response to viral proteins limited use of these vectors. Hardy et al. (S. Hardy, M. Kitamura, T. Harris-Stansil, Y. Dai, and M. L. Phipps, J Virol 71:1842–1849, 1997, http://jvi.asm.org/content/71/3/1842.abstract) described the use of Cre-lox recombination to address these problems. These authors described a simple method for constructing E1-substituted adenoviruses as well as a method to construct adenovirus vectors carrying recombinant genes in place of all of the viral genes, called gutless adenovirus vectors. The only viral sequences included in the gutless vector are those needed in cis for replication and packaging. The authors presented one application for constructing new E1-substituted adenoviruses in which the viruses are almost pure without plaque purification, producing a working stock of virus for initial experiments in 10 days. In a second application, a negatively selected helper virus can be used to support the growth of an adenovirus with all viral coding sequences deleted. This system can produce highly enriched gutless virus preparations for gene therapy. Highly Efficient and Sustained Gene Transfer in Adult Neurons with a Lentivirus Vector Blömer et al. (U. Blömer et al., J Virol 71:6641– 6649, 1997, http://jvi.asm.org/content/ 71/9/6641.abstract) investigated the use of a lentivirus-based vector capable of infecting dividing and quiescent cells for gene delivery in vivo by injecting a highly concentrated viral vector stock into the striatum and hippocampus of adult rats. Control brains were injected with a Moloney murine leukemia virus, adenovirus, or adeno-associated virus vector. Lentivirus vectors based on human immunodeficiency virus (HIV) can infect and stably transduce dividing as well as terminally differentiated cells. The efficiency of infection by the lentivirus vector was improved by deoxynucleoside triphosphate pretreatment of the vector and was reduced by mutation of integrase and the Vpr-matrix protein complex involved in the nuclear translocation of the preintegration complex. The lentivirus vector system was able to efficiently and stably infect quiescent cells in the primary injection site with transgene expression for over 6 months. Further, labeling experiments showed that striatal cells transduced by the lentivirus vector were terminally differentiated neurons.

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Classic Spotlight, 1996 and 1997: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors.

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