Rol del virus sincicial respiratorio en una cohorte de adultos mayores / Respiratory Syncytial Virus in the elderly adults

El rol de los virus respiratorios distintos de influenza en las infecciones respiratorias agudas en los adultos mayores ha sido probablemente subestimado. En los últimos años, los avances en técnicas moleculares de diagnóstico han hecho posible la identificación rápida del virus sincicial respiratorio humano (HRSV). Realizamos un estudio prospectivo observacional para evaluar el rol del HRSV en mayores de 65 años que se hospitalizaron por infecciones respiratorias en nuestra institución, ubicada en la ciudad de La Plata, provincia de Buenos Aires. Fueron reclutados 124 pacientes y el HRSV se detectó en 13, influenza B en 9 e influenza A en 8. La presentación clínica más frecuente de los The role of respiratory viruses other than influenza in acute respiratory tract infections among elderly adults has probably been underestimated. Recent advances in molecular diagnosis have made the rapid identification of human respiratory syncitial virus HRSV infection possible. We conducted a prospective observational study to evaluate the role of HRSV in elderly patients (>65 years of age) hospitalized for acute respiratory infections. A total of 124 patients were recruited, HRSV infection was identified in 13 patients, Influenza B in 9 patients and influenza A in 8 patients. The most frequent clinical presentation was bronchospasm and the infection was prevalent in patients with comorbidities. HRSV infections accounted for an important number of hospital admissions and has been associated with high mortality rates (23%). pacientes con HRSV fue el broncoespasmo y afectó principalmente a personas con comorbilidades. HRSV fue responsable de un número importante de internaciones por enfermedad respiratoria aguda en mayores de 65 años en nuestra institución y se asoció a mortalidad elevada (23%).

The role of respiratory viruses other than influenza in acute respiratory tract infections among elderly adults has probably been underestimated. Recent advances in molecular diagnosis have made the rapid identification of human respiratory syncitial virus HRSV infection possible. We conducted a prospective observational study to evaluate the role of HRSV in elderly patients (>65 years of age) hospitalized for acute respiratory infections. A total of 124 patients were recruited, HRSV infection was identified in 13 patients, Influenza B in 9 patients and influenza A in 8 patients. The most frequent clinical presentation was bronchospasm and the infection was prevalent in patients with comorbidities. HRSV infections accounted for an important number of hospital admissions and has been associated with high mortality rates (23%).

Vaccines for the Paramyxoviruses and Pneumoviruses: Successes, Candidates, and Hurdles.

Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children within the first few years of life and are the etiologic agents for many serious acute respiratory illnesses. These virus infections are also associated with long-term diseases that impact quality of life, including asthma. Despite over a half-century of vaccine research, development, and clinical trials, no vaccine has been licensed to date for the paramyxoviruses or pneumoviruses for the youngest infants. In this study, we describe the recent reclassification of paramyxoviruses and pneumoviruses into distinct families by the International Committee on the Taxonomy of Viruses. We also discuss some past unsuccessful vaccine trials and some currently preferred vaccine strategies. Finally, we discuss hurdles that must be overcome to support successful respiratory virus vaccine development for the youngest children.

Generation of monoclonal antibodies specific of the postfusion conformation of the Pneumovirinae fusion (F) protein.

Paramyxovirus entry into cells requires fusion of the viral and cell membranes mediated by one of the major virus glycoproteins, the fusion (F) glycoprotein which transits from a metastable pre-fusion conformation to a highly stable post-fusion structure during the membrane fusion process. F protein refolding involves large conformational changes of the protein trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) from each protomer into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of the Pneumovirinae F proteins, and as extension of previous work (Palomo et al., 2014), a general strategy was designed to obtain polyclonal and particularly monoclonal antibodies specific of the 6HB motif of the Pneumovirinae fusion protein. The antibodies reported here should assist in the characterization of the structural changes that the F protein of human metapneumovirus or respiratory syncytial virus experiences during the process of membrane fusion.

The Pneumovirinae fusion (F) protein: A common target for vaccines and antivirals.

The Pneumovirinae fusion (F) protein mediates fusion of the virus and cell membrane, an essential step for entry of the viral genome in the cell cytoplasm and initiation of a new infectious cycle. Accordingly, potent inhibitors of virus infectivity have been found among antibodies and chemical compounds that target the Pneumovirinae F protein. Recent developments in structure-based vaccines have led to a deeper understanding of F protein antigenicity, unveiling new conformations and epitopes which should assist in development of efficacious vaccines. Similarly, structure-based studies of potent antiviral inhibitors have provided information about their mode of action and mechanisms of resistance. The advantages and disadvantages of the different options to battle against important pathogens, such as human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are summarized and critically discussed in this review.

Generation of Tioman virus nucleocapsid-like particles in yeast Saccharomyces cerevisiae.

Tioman virus (TioV) was isolated from a number of pooled urine samples of Tioman Island flying foxes (Pteropus hypomelanus) during the search for the reservoir host of Nipah virus. Studies have established TioV as a new virus in the family Paramyxoviridae. This novel paramyxovirus is antigenically related to Menangle virus that was isolated in Australia in 1997 during disease outbreak in pigs. TioV causes mild disease in pigs and has a predilection for lymphoid tissues. Recent serosurvey showed that 1.8% of Tioman Islanders had neutralizing antibodies against TioV, indicating probable past infection. For the development of convenient serological tests for this virus, recombinant TioV nucleocapsid (N) protein was expressed in the yeast Saccharomyces cerevisiae. High yields of recombinant TioV N protein were obtained. Electron microscopy demonstrated that purified recombinant N protein self-assembled into nucleocapsid-like particles which were identical in density and morphology to authentic nucleocapsids from paramyxovirus-infected cells. Different size nucleocapsid-like particles were stable and readily purified by CsCl gradient ultracentrifugation. Polyclonal sera raised in rabbits after immunization with recombinant TioV N protein reacted reliably with TioV infected tissues in immunohistochemistry tests. It confirmed that the antigenic properties of yeast derived TioV N protein are identical to authentic viral protein.

A wild goose metapneumovirus containing a large attachment glycoprotein is avirulent but immunoprotective in domestic turkeys.

The genomic structure and composition of an avian metapneumovirus (aMPV) recently isolated from wild Canada geese (goose 15a/01) in the United States, together with its replication, virulence, and immunogenicity in domestic turkeys, were investigated. The sizes of seven of the eight genes, sequence identity, and genome organization of goose aMPV were similar to those of turkey aMPV subtype C (aMPV/C) strains, indicating that it belonged to the subtype. However, the goose virus contained the largest attachment (G) gene of any pneumovirus or metapneumovirus, with the predicted G protein of 585 amino acids (aa) more than twice the sizes of G proteins from other subtype C viruses and human metapneumovirus and more than 170 aa larger than the G proteins from the other aMPV subtypes (subtypes A, B, and D). The large G gene resulted from a 1,015-nucleotide insertion at 18 nucleotides upstream of the termination signal of the turkey aMPV/C G gene. Three other aMPV isolates from Canada geese had similarly large G genes, whereas analysis of recent aMPV strains circulating in U.S. turkeys did not indicate the presence of the goose virus-like strain. In vitro, the goose virus replicated to levels (2 x 10(5) to 5 x 10(5) 50% tissue culture infective dose) comparable to those produced by turkey aMPV/C strains. More importantly, the virus replicated efficiently in the upper respiratory tract of domestic turkeys but with no clinical signs in either day-old or 2-week-old turkeys. The virus was also horizontally transmitted to naïve birds, and turkey infections with goose 15a/01 induced production of aMPV-specific antibodies. Challenging day-old or 2-week-old turkeys vaccinated with live goose aMPV resulted in lower clinical scores in 33% of the birds, whereas the rest of the birds had no detectable clinical signs of the upper respiratory disease, suggesting that the mutant virus may be a safe and effective vaccine against aMPV infection outbreaks in commercial turkeys.