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46 results on '"Rima, Bert K"'

1. Human parainfluenza virus evolution during lung infection of immunocompromised individuals promotes viral persistence

Author

Greninger, Alexander L., Rybkina, Ksenia, Lin, Michelle J., Drew-Bear, Jennifer, Marcink, Tara C., Shean, Ryan C., Makhsous, Negar, Boeckh, Michael, Harder, Olivia, Bovier, Francesca, Burstein, Shana R., Niewiesk, Stefan, Rima, Bert K., Porotto, Matteo, and Moscona, Anne

Subjects
Diagnosis, Care and treatment, Analysis, Risk factors, Health aspects, Immunocompromised host -- Health aspects, Amino acids -- Analysis, Parainfluenza viruses -- Diagnosis -- Care and treatment -- Risk factors, Lung diseases -- Risk factors -- Diagnosis -- Care and treatment
Abstract

Introduction Human parainfluenza virus 3 (HPIV3) accounts for a large proportion of respiratory illness in humans, especially in children, the elderly, and immunocompromised individuals (1-9), yet there is currently no [...], The capacity of respiratory viruses to undergo evolution within the respiratory tract raises the possibility of evolution under the selective pressure of the host environment or drug treatment. Long-term infections in immunocompromised hosts are potential drivers of viral evolution and development of infectious variants. We showed that intrahost evolution in chronic human parainfluenza virus 3 (HPIV3) infection in immunocompromised individuals elicited mutations that favored viral entry and persistence, suggesting that similar processes may operate across enveloped respiratory viruses. We profiled longitudinal HPIV3 infections from 2 immunocompromised individuals that persisted for 278 and 98 days. Mutations accrued in the HPIV3 attachment protein hemagglutinin-neuraminidase (HN), including the first in vivo mutation in HN's receptor binding site responsible for activating the viral fusion process. Fixation of this mutation was associated with exposure to a drug that cleaves host-cell sialic acid moieties. Longitudinal adaptation of HN was associated with features that promote viral entry and persistence in cells, including greater avidity for sialic acid and more active fusion activity in vitro, but not with antibody escape. Long-term infection thus led to mutations promoting viral persistence, suggesting that host-directed therapeutics may support the evolution of viruses that alter their biophysical characteristics to persist in the face of these agents in vivo.

Published
2021
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8. Recombinant Subgroup B Human Respiratory Syncytial Virus Expressing Enhanced Green Fluorescent Protein Efficiently Replicates in Primary Human Cells and Is Virulent in Cotton Rats

Author

Lemon, Ken, primary, Nguyen, D. Tien, additional, Ludlow, Martin, additional, Rennick, Linda J., additional, Yüksel, Selma, additional, van Amerongen, Geert, additional, McQuaid, Stephen, additional, Rima, Bert K., additional, de Swart, Rik L., additional, and Duprex, W. Paul, additional

Published
2015
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12. Virus species polemics: 14 senior virologists oppose a proposed change to the ICTV definition of virus species

Author

Van Regenmortel, Marc H. V., primary, Ackermann, Hans-Wolfgang, additional, Calisher, Charles H., additional, Dietzgen, Ralf G., additional, Horzinek, Marian C., additional, Keil, Gunther M., additional, Mahy, Brian W. J., additional, Martelli, Giovanni P., additional, Murphy, Frederick A., additional, Pringle, Craig, additional, Rima, Bert K., additional, Skern, Tim, additional, Vetten, H.-J., additional, and Weaver, Scott C., additional

Published
2012
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13. The innate antiviral factor APOBEC3G targets replication of measles, mumps and respiratory syncytial viruses

Author

Fehrholz, Markus, primary, Kendl, Sabine, additional, Prifert, Christiane, additional, Weissbrich, Benedikt, additional, Lemon, Ken, additional, Rennick, Linda, additional, Duprex, Paul W., additional, Rima, Bert K., additional, Koning, Fransje A., additional, Holmes, Rebecca K., additional, Malim, Michael H., additional, and Schneider-Schaulies, Jürgen, additional

Published
2012
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23. Using Green Fluorescent Protein to Monitor Measles Virus Cell-to-Cell Spread by Time-Lapse Confocal Microscopy.

Author

Walker, John M., Hicks, Barry W., Duprex, W. Paul, and Rima, Bert K.

Abstract

The mechanisms by which viruses enter cells have been, and remain, an area of intensive study. Attaining a more comprehensive understanding of the mechanisms involved in cell attachment, penetration, and delivery of the genome into the cytoplasm or nucleus of the cell has potentially far-reaching implications for the prevention and therapy of virus infections. Similarly, elucidating the processes by which viruses spread from infected to uninfected cells within the host may also assist in the rational development of novel treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2002
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32. MORBILLIVIRUS INFECTION IN MANATEES

Author

Duignan, Padraig J., primary, House, Carol, additional, Walsh, Michael T., additional, Campbell, Terry, additional, Bossart, Gregory D., additional, Duffy, Noel, additional, Fernandes, Peter J., additional, Rima, Bert K., additional, Wright, Scott, additional, and Geraci, Joseph R., additional

Published
1995
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41. Morbillivirus infection in manatees

Author

House, Carol, Duignan, Padraig J., Geraci, Joseph R., Duffy, Noel, Campbell, Terry, Walsh, Michael T., Bossart, Gregory D., Wright, Scott, Fernandes, Peter J., and Rima, Bert K.

Subjects
DISEASES
Published
1995

42. Human parainfluenza virus evolution during lung infection of immunocompromised individuals promotes viral persistence

Author

Shana R Burstein, Bert K. Rima, Jennifer Drew-Bear, Stefan Niewiesk, Michael Boeckh, Tara C. Marcink, Olivia Harder, Alexander L. Greninger, Michelle J. Lin, Matteo Porotto, Ksenia Rybkina, Ryan C. Shean, Negar Makhsous, Anne Moscona, Francesca T. Bovier, Greninger, Alexander L, Rybkina, Ksenia, Lin, Michelle J, Drew-Bear, Jennifer, Marcink, Tara C, Shean, Ryan C, Makhsous, Negar, Boeckh, Michael, Harder, Olivia, Bovier, Francesca, Burstein, Shana R, Niewiesk, Stefan, Rima, Bert K, Porotto, Matteo, and Moscona, Anne

Subjects
Adult, Lung Diseases, DNA Mutational Analysis, Graft vs Host Disease, Biology, medicine.disease_cause, chemistry.chemical_compound, Immunocompromised Host, Young Adult, Gene Frequency, Viral entry, Virology, medicine, Humans, Avidity, Lung, Sirolimus, Mutation, Binding Sites, Paramyxoviridae Infections, General Medicine, Mycophenolic Acid, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Virus Internalization, Influenza, N-Acetylneuraminic Acid, Sialic acid, Parainfluenza Virus 3, Human, Human Parainfluenza Virus, Leukemia, Myeloid, Acute, medicine.anatomical_structure, HEK293 Cells, chemistry, Viral evolution, biology.protein, Receptors, Virus, Female, Antibody, Viral Fusion Proteins, Respiratory tract, Research Article
Abstract

The capacity of respiratory viruses to undergo evolution within the respiratory tract raises the possibility of evolution under the selective pressure of the host environment or drug treatment. Long-term infections in immunocompromised hosts are potential drivers of viral evolution and development of infectious variants. We showed that intrahost evolution in chronic human parainfluenza virus 3 (HPIV3) infection in immunocompromised individuals elicited mutations that favored viral entry and persistence, suggesting that similar processes may operate across enveloped respiratory viruses. We profiled longitudinal HPIV3 infections from 2 immunocompromised individuals that persisted for 278 and 98 days. Mutations accrued in the HPIV3 attachment protein hemagglutinin-neuraminidase (HN), including the first in vivo mutation in HN’s receptor binding site responsible for activating the viral fusion process. Fixation of this mutation was associated with exposure to a drug that cleaves host-cell sialic acid moieties. Longitudinal adaptation of HN was associated with features that promote viral entry and persistence in cells, including greater avidity for sialic acid and more active fusion activity in vitro, but not with antibody escape. Long-term infection thus led to mutations promoting viral persistence, suggesting that host-directed therapeutics may support the evolution of viruses that alter their biophysical characteristics to persist in the face of these agents in vivo.

Published
2021

43. Determination of Spontaneous Mutation Frequencies in Measles Virus under Nonselective Conditions.

Author

Xiaomeng Zhang, Rennick, Linda J., Duprex, W. Paul, and Rima, Bert K.

Subjects
*MEASLES, *MONOCLONAL antibodies, *GENETIC mutation, *GREEN fluorescent protein, *TRANSCRIPTION factors
Abstract

There is a paradox between the remarkable genetic stability of measles virus (MV) in the field and the high mutation rates implied by the frequency of the appearance of monoclonal antibody escape mutants generated when the virus is pressured to revert in vitro (S. J. Schrag, P. A. Rota, and W. J. Bellini, J. Virol. 73:51-54, 1999). We established a highly sensitive assay to determine frequencies of various categories of mutations in large populations of wild-type and laboratory-adapted MVs using recombinant viruses containing an additional transcription unit (ATU) encoding enhanced green fluorescent protein (EGFP). Single and double mutations were made in the fluorophore of EGFP to ablate fluorescence. The frequencies of reversion mutants in the population were determined by measuring the appearance of fluorescence indicating a revertant virus. This allows mutation rates to be measured under nonselective conditions, as phenotypic reversion to fluorescence requires only either a single- or a double-nucleotide change and amino acid substitution, which does not affect the length of the nonessential reporter protein expressed from the ATU. Mutation rates in MV are the same for wild-type and laboratory-adapted viruses, and they are an order of magnitude lower than the previous measurement assessed under selective conditions. The actual mutation rate for MV is approximately 1.8 x 10-6 per base per replication event. [ABSTRACT FROM AUTHOR]

Published
2013
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44. Features of Circulating Parainfluenza Virus Required for Growth in Human Airway

Author

Anne Moscona, Nora C. Toussaint, Soren Germer, Laura M. Palermo, Lucy Skrabanek, Bert K. Rima, Stefan Niewiesk, Paul Zumbo, Manik Uppal, Devra Huey, Matteo Porotto, Palermo, Laura M., Uppal, Manik, Skrabanek, Lucy, Zumbo, Paul, Germer, Soren, Toussaint, Nora C., Rima, Bert K., Huey, Devra, Niewiesk, Stefan, Porotto, Matteo, and Moscona, Anne

Subjects
0301 basic medicine, food.ingredient, viruses, Respiratory System, Virulence, Genome, Viral, Biology, Respirovirus, Respirovirus Infections, Microbiology, Virus, 03 medical and health sciences, food, Viral entry, Virology, Animals, Humans, Sigmodontinae, Animal, Sequence Analysis, DNA, Virus Internalization, Respirovirus Infection, QR1-502, 3. Good health, Human Parainfluenza Virus, 030104 developmental biology, Respiratory virus, Immortalised cell line, Research Article, Human, Respiroviru
Abstract

Respiratory paramyxoviruses, including the highly prevalent human parainfluenza viruses, cause the majority of childhood croup, bronchiolitis, and pneumonia, yet there are currently no vaccines or effective treatments. Paramyxovirus research has relied on the study of laboratory-adapted strains of virus in immortalized cultured cell lines. We show that findings made in such systems about the receptor interaction and viral fusion requirements for entry and fitness—mediated by the receptor binding protein and the fusion protein—can be drastically different from the requirements for infection in vivo. Here we carried out whole-genome sequencing and genomic analysis of circulating human parainfluenza virus field strains to define functional and structural properties of proteins of circulating strains and to identify the genetic basis for properties that confer fitness in the field. The analysis of clinical strains suggests that the receptor binding-fusion molecule pairs of circulating viruses maintain a balance of properties that result in an inverse correlation between fusion in cultured cells and growth in vivo. Future analysis of entry mechanisms and inhibitory strategies for paramyxoviruses will benefit from considering the properties of viruses that are fit to infect humans, since a focus on viruses that have adapted to laboratory work provides a distinctly different picture of the requirements for the entry step of infection., IMPORTANCE Mechanistic information about viral infection—information that impacts antiviral and vaccine development—is generally derived from viral strains grown under laboratory conditions in immortalized cells. This study uses whole-genome sequencing of clinical strains of human parainfluenza virus 3—a globally important respiratory paramyxovirus—in cell systems that mimic the natural human host and in animal models. By examining the differences between clinical isolates and laboratory-adapted strains, the sequence differences are correlated to mechanistic differences in viral entry. For this ubiquitous and pathogenic respiratory virus to infect the human lung, modulation of the processes of receptor engagement and fusion activation occur in a manner quite different from that carried out by the entry glycoprotein-expressing pair of laboratory strains. These marked contrasts in the viral properties necessary for infection in cultured immortalized cells and in natural host tissues and animals will influence future basic and clinical studies.

Published
2016
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