Viktor Müller
Editorial: A Plea for Caution: Huge Risks Associated with Lab-bred Flu
Viruses 2012, 4(2), 276-279; doi:10.3390/v4020276 - published online 7 February 2012
Show/Hide AbstractAbstract: I wish to express concern about the maintenance of laboratory strains of H5N1 influenza viruses that might be adapted for transmission among humans.

Catherine L. Hunt , Nicholas J. Lennemann and Wendy Maury
Review: Filovirus Entry: A Novelty in the Viral Fusion World
Viruses 2012, 4(2), 258-275; doi:10.3390/v4020258 - published online 7 February 2012
Show/Hide AbstractAbstract: Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein₁ subunit (GP₁) with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP₁ is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS). Details of the molecular events following cathepsin-dependent trimming of GP₁ are currently incomplete; however, the processed GP₁ specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. Additional events such as further GP₁ processing and/or reducing events may also be required to generate a fusion-ready form of the glycoprotein. Once this has been achieved, sequences in the filovirus GP₂ subunit mediate viral/cellular membrane fusion via mechanisms similar to those previously described for other enveloped viruses. This multi-step entry pathway highlights the complex and highly orchestrated path of internalization and fusion that appears unique for filoviruses.

Stephen J. O’Brien , Jennifer L. Troyer , Meredith A. Brown , Warren E. Johnson , Agostinho Antunes , Melody E. Roelke and Jill Pecon-Slattery
Review: Emerging Viruses in the Felidae: Shifting Paradigms
Viruses 2012, 4(2), 236-257; doi:10.3390/v4020236 - published online 7 February 2012
Show/Hide AbstractAbstract: The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.

Robyn N. Hall , Joanne Meers , Elizabeth Fowler and Timothy Mahony
Review: Back to BAC: The Use of Infectious Clone Technologies for Viral Mutagenesis
Viruses 2012, 4(2), 211-235; doi:10.3390/v4020211 - published online 3 February 2012
Show/Hide AbstractAbstract: Bacterial artificial chromosome (BAC) vectors were first developed to facilitate the propagation and manipulation of large DNA fragments in molecular biology studies for uses such as genome sequencing projects and genetic disease models. To facilitate these studies, methodologies have been developed to introduce specific mutations that can be directly applied to the mutagenesis of infectious clones (icBAC) using BAC technologies. This has resulted in rapid identification of gene function and expression at unprecedented rates. Here we review the major developments in BAC mutagenesis in vitro. This review summarises the technologies used to construct and introduce mutations into herpesvirus icBAC. It also explores developing technologies likely to provide the next leap in understanding these important viruses.

Adriana Landa-Cardeña , Jaime Morales-Romero , Rebeca García-Roman , Ana Georgina Cobián-Güemes , Ernesto Méndez , Cristina Ortiz-Leon , Felipe Pitalúa-Cortés , Silvia Ivonne Mora and Hilda Montero
Article: Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico
Viruses 2012, 4(2), 200-210; doi:10.3390/v4020200 - published online 25 January 2012
Show/Hide AbstractAbstract: Human rhinovirus (HRV) is a leading cause of acute respiratory infection (ARI) in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR) of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.

Hind J. Fadel , Dyana T. Saenz and Eric M. Poeschla
Article: Construction and Testing of orfA +/- FIV Reporter Viruses
Viruses 2012, 4(1), 184-199; doi:10.3390/v4010184 - published online 23 January 2012
Show/Hide AbstractAbstract: Single cycle reporter viruses that preserve the majority of the HIV-1 genome, long terminal repeat-promoted transcription and Rev-dependent structural protein expression are useful for investigating the viral life cycle. Reporter viruses that encode the viral proteins in cis in this way have been lacking for feline immunodeficiency virus (FIV), where the field has used genetically minimized transfer vectors with viral proteins supplied in trans. Here we report construction and use of a panel of single cycle FIV reporter viruses that express fluorescent protein markers. The viruses can be produced to high titer using human cell transfection and can transduce diverse target cells. To illustrate utility, we tested versions that are (+) and (-) for OrfA, an FIV accessory protein required for replication in primary lymphocytes and previously implicated in down-regulation of the primary FIV entry receptor CD134. We observed CD134 down-regulation after infection with or without OrfA, and equivalent virion production as well. These results suggest a role for FIV proteins besides Env or OrfA in CD134 down-regulation.