Viruses2013, 5(12), 3007-3020; doi:10.3390/v5123007 - published online 4 December 2013 Show/Hide Abstract
Abstract: To gain comprehensive genetic information of circulating avian coronavirus infectious bronchitis virus (IBV) isolates in China, analysis of the phylogenetic tree, entropy of the amino acid sequences, and the positive selection as well as computational recombinations of S1, M and N genes of 23 IBV isolates was conducted in the present study. The phylogenetic trees based on the S1, M and N genes exhibited considerably different topology and the CK/CH/LSC/99I-type isolates were the predominant IBVs based on the phylogenetic analysis of S1 gene. Results of entropy of amino acid sequences revealed that the S1 gene had the largest variation; the M gene had less variation than the N gene. Positive selections were detected in not only S1 but also M and N gene proteins. In addition, five S1 gene recombinants between vaccine strain 4/91 and CK/CH/LSC/99I-type field isolate were confirmed. In conclusion, multiple IBV genotypes co-circulated; genetic diversity and positive selections existed in S1, M and N genes; 4/91 vaccine recombinants emerged in China. Our results show that field IBVs in China are continuing to evolve and vaccine strains may have an important role in the appearance of new IBV strains via recombination. In addition, the present study indicates that IBV evolution is driven by both generations of genetic diversity and selection.
Viruses2013, 5(12), 2977-3006; doi:10.3390/v5122977 - published online 3 December 2013 Show/Hide Abstract
Abstract: The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.
Viruses2013, 5(12), 2963-2976; doi:10.3390/v5122963 - published online 2 December 2013 Show/Hide Abstract
Abstract: Equine infectious anemia (EIA), identified in 1843  as an infectious disease of horses and as a viral infection in 1904, remains a concern in veterinary medicine today. Equine infectious anemia virus (EIAV) has served as an animal model of HIV-1/AIDS research since the original identification of HIV. Similar to other lentiviruses, EIAV has a high propensity for genomic sequence and antigenic variation, principally in its envelope (Env) proteins. However, EIAV possesses a unique and dynamic disease presentation that has facilitated comprehensive analyses of the interactions between the evolving virus population, progressive host immune responses, and the definition of viral and host correlates of immune control and vaccine efficacy. Summarized here are key findings in EIAV that have provided important lessons toward understanding long term immune control of lentivirus infections and the parameters for development of an enduring broadly protective AIDS vaccine.
Viruses2013, 5(12), 2946-2962; doi:10.3390/v5122946 - published online 28 November 2013 Show/Hide Abstract
Abstract: The combination of genetic modification and hematopoietic stem cell (HSC) transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.
Viruses2013, 5(12), 2931-2945; doi:10.3390/v5122931 - published online 28 November 2013 Show/Hide Abstract
Abstract: ToChLPV and PepGMV are Begomoviruses that have adapted to a wide host range and are able to cause major diseases in agronomic crops. We analyzed the efficacy of induced resistance to PepGMV in Nicotiana benthamiana plants with two constructs: one construct with homologous sequences derived from PepGMV, and the other construct with heterologous sequences derived from ToChLPV. Plants protected with the heterologous construct showed an efficacy to decrease the severity of symptoms of 45%, while plants protected with the homologous construct showed an efficacy of 80%. Plants protected with the heterologous construct showed a reduction of incidence of 42.86%, while the reduction of incidence in plants protected with the homologous construct was 57.15%. The efficacy to decrease viral load was 95.6% in plants protected with the heterologous construct, and 99.56% in plants protected with the homologous construct. We found, in both constructs, up-regulated key components of the RNAi pathway. This demonstrates that the efficacy of the constructs was due to the activation of the gene silencing mechanism, and is reflected in the decrease of viral genome copies, as well as in recovery phenotype. We present evidence that both constructs are functional and can efficiently induce transient resistance against PepGMV infections. This observation guarantees a further exploration as a strategy to control complex Begomovirus diseases in the field.
Viruses2013, 5(12), 2920-2930; doi:10.3390/v5122920 - published online 27 November 2013 Show/Hide Abstract
Abstract: Giant viruses and amoebae are common in freshwater, where they can coexist with other living multicellular organisms. We screened leeches from the species Hirudo medicinalis for giant viruses. We analyzed five H. medicinalis obtained from Tunisia (3) and France (2). The leeches were decontaminated and then dissected to remove internal parts for co-culture with Acanthamoeba polyphaga. The genomes of isolated viruses were sequenced on a 454 Roche instrument, and a comparative genomics analysis was performed. One Mimivirus was isolated and the strain was named Hirudovirus. The genome assembly generated two scaffolds, which were 1,155,382 and 25,660 base pairs in length. Functional annotations were identified for 47% of the genes, which corresponds to 466 proteins. The presence of Mimividae in the same ecological niche as wild Hirudo may explain the presence of the mimivirus in the digestive tract of the leech, and several studies have already shown that viruses can persist in the digestive tracts of leeches fed contaminated blood. As leeches can be used medically and Mimiviruses have the potential to be an infectious agent in humans, patients treated with leeches should be surveyed to investigate a possible connection.