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Recombinant viruses expressing reporter fluorescent or bioluminescent proteins are an excellent option to evaluate the dynamics of viral infection progression in both cultured cells and/or validated animal models of viral infection. Reporter proteins are valid surrogates for direct detection of infected cells in vitro and in vivo, without the use of secondary methodologies to identify infected cells. By eliminating the need of secondary labeling, tractable replicating-competent, reporter-expressing viruses provide an ideal approach to monitor viral infections in real time, representing a significant advance in the study of the biology of viruses, to evaluate vaccination approaches, and to identify new therapeutics against viral infections using high-throughput screening settings. In this Special Issue "Replication-Competent Reporter-Expressing Viruses" we review replication-competent, reporter-expressing viruses belonging to different families, methods of characterization, and applications to facilitate the study of in vitro and in vivo viral infections. We also seek to discuss disadvantages and limitations associated with these reporter-expressing viruses. Finally, we provide rational future perspectives and additional avenues for the development, characterization, and applications of recombinant, reporter-expressing, competent viruses.

Recombinant viruses. --- Genetically engineered viruses --- Viruses --- Recombinant microorganisms --- Genetic engineering

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Annotation Recombinant viruses expressing reporter fluorescent or bioluminescent proteins are an excellent option to evaluate the dynamics of viral infection progression in both cultured cells and/or validated animal models of viral infection. Reporter proteins are valid surrogates for direct detection of infected cells in vitro and in vivo, without the use of secondary methodologies to identify infected cells. By eliminating the need of secondary labeling, tractable replicating-competent, reporter-expressing viruses provide an ideal approach to monitor viral infections in real time, representing a significant advance in the study of the biology of viruses, to evaluate vaccination approaches, and to identify new therapeutics against viral infections using high-throughput screening settings. In this Special Issue "Replication-Competent Reporter-Expressing Viruses" we review replication-competent, reporter-expressing viruses belonging to different families, methods of characterization, and applications to facilitate the study of in vitro and in vivo viral infections. We also seek to discuss disadvantages and limitations associated with these reporter-expressing viruses. Finally, we provide rational future perspectives and additional avenues for the development, characterization, and applications of recombinant, reporter-expressing, competent viruses.

Recombinant viruses.

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Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders—including fetal microcephaly and Guillain-Barré syndrome in adults—have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus–host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis.

microRNAs --- antivirals --- reverse genetics --- nucleic acid computation --- viral pathogenesis --- plaque reduction neutralization test --- clinical trials --- viral genetic variation --- viral fitness --- pregnancy --- type I IFN antagonist --- prM-E proteins --- eye --- replicon --- antiviral responses --- Bacterial artificial chromosome --- gene expression --- NS1 protein --- viral permissiveness --- ZIKV–host interactions --- reporter virus --- viral persistence --- blood-retinal barrier --- virus like particles --- emerging arbovirus --- Non-human primates --- heme-oxygenase 1 --- mosquito surveillance --- antiviral compounds --- ZIKV-associated neurologic disorders --- external quality assessment --- outbreak control --- therapeutics --- cryptic promoter silencing --- testis --- neurons --- mutagenesis --- RNA-seq --- microsphere immunoassay --- host-directed antivirals --- molecular diagnostics --- Bayesian analyses --- astrocytomas --- Full-length cDNA infectious clones --- viral pathogenicity --- neural progenitor cells --- full-length molecular clone --- antiviral --- multiplex nucleic acid detection --- Asian-lineage --- nucleic acid strand exchange --- IgA --- African-lineage --- vaccines --- Zika --- research models and tools --- immune response --- IgG avidity tests --- polymerase chain reaction --- Asian lineage --- sexual transmission --- TLR7/8 --- neuropathogenesis --- cross-reactions --- genetic variability --- mosquito --- ZIKV --- infectious cDNA --- prostate --- host genetic variation --- monoclonal antibodies --- optimised --- anti-viral immunity --- QCMD --- arbovirus --- FSS13025 --- MR766 --- NS5 --- EQA --- testicular cells --- virus attachment --- flavivirus --- mosquito-borne flavivirus --- dsRNA --- boolean logic-processing nucleic acid probes --- Ziks virus --- viral replication --- Aedes aegypti --- infection --- natural history --- infectious RNA --- zika virus --- chimeric viruses --- subgenomic replicon --- replication --- human brain glial cells --- microglia cells --- hepatocytes --- bacterial artificial chromosome --- detoxification and immune system responses --- testes --- dengue viruses --- Zika virus --- insecticide resistance --- NS2A protein --- plasmid toxicity --- cell surface receptors --- serology --- viral evolution --- laboratory preparedness --- flaviviruses --- Tet-inducible --- dengue virus --- diagnosis --- assay standardization --- infectious clone --- ELISA --- innate response --- congenital Zika syndrome --- secondary infections --- apoptosis --- viral survival --- ocular --- validated --- rhesus macaques --- neuroinflammation --- placenta cells --- NHP --- Zika virus (ZIKV) --- point-of-care diagnostics --- isothermal nucleic acid amplification --- microcephaly --- cytopathic effects --- indirect immunofluorescence --- fetal infection --- therapy --- siRNA --- viral counteraction --- neural cells --- silvestrol --- eIF4A

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Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders—including fetal microcephaly and Guillain-Barré syndrome in adults—have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus–host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis.

microRNAs --- antivirals --- reverse genetics --- nucleic acid computation --- viral pathogenesis --- plaque reduction neutralization test --- clinical trials --- viral genetic variation --- viral fitness --- pregnancy --- type I IFN antagonist --- prM-E proteins --- eye --- replicon --- antiviral responses --- Bacterial artificial chromosome --- gene expression --- NS1 protein --- viral permissiveness --- ZIKV–host interactions --- reporter virus --- viral persistence --- blood-retinal barrier --- virus like particles --- emerging arbovirus --- Non-human primates --- heme-oxygenase 1 --- mosquito surveillance --- antiviral compounds --- ZIKV-associated neurologic disorders --- external quality assessment --- outbreak control --- therapeutics --- cryptic promoter silencing --- testis --- neurons --- mutagenesis --- RNA-seq --- microsphere immunoassay --- host-directed antivirals --- molecular diagnostics --- Bayesian analyses --- astrocytomas --- Full-length cDNA infectious clones --- viral pathogenicity --- neural progenitor cells --- full-length molecular clone --- antiviral --- multiplex nucleic acid detection --- Asian-lineage --- nucleic acid strand exchange --- IgA --- African-lineage --- vaccines --- Zika --- research models and tools --- immune response --- IgG avidity tests --- polymerase chain reaction --- Asian lineage --- sexual transmission --- TLR7/8 --- neuropathogenesis --- cross-reactions --- genetic variability --- mosquito --- ZIKV --- infectious cDNA --- prostate --- host genetic variation --- monoclonal antibodies --- optimised --- anti-viral immunity --- QCMD --- arbovirus --- FSS13025 --- MR766 --- NS5 --- EQA --- testicular cells --- virus attachment --- flavivirus --- mosquito-borne flavivirus --- dsRNA --- boolean logic-processing nucleic acid probes --- Ziks virus --- viral replication --- Aedes aegypti --- infection --- natural history --- infectious RNA --- zika virus --- chimeric viruses --- subgenomic replicon --- replication --- human brain glial cells --- microglia cells --- hepatocytes --- bacterial artificial chromosome --- detoxification and immune system responses --- testes --- dengue viruses --- Zika virus --- insecticide resistance --- NS2A protein --- plasmid toxicity --- cell surface receptors --- serology --- viral evolution --- laboratory preparedness --- flaviviruses --- Tet-inducible --- dengue virus --- diagnosis --- assay standardization --- infectious clone --- ELISA --- innate response --- congenital Zika syndrome --- secondary infections --- apoptosis --- viral survival --- ocular --- validated --- rhesus macaques --- neuroinflammation --- placenta cells --- NHP --- Zika virus (ZIKV) --- point-of-care diagnostics --- isothermal nucleic acid amplification --- microcephaly --- cytopathic effects --- indirect immunofluorescence --- fetal infection --- therapy --- siRNA --- viral counteraction --- neural cells --- silvestrol --- eIF4A