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Effect of hemagglutinin-neuraminidase inhibitors BCX 2798 and BCX 2855 on growth and pathogenicity of Sendai/human parainfluenza type 3 chimera virus in mice.
Watanabe M, Mishin VP, Brown SA, Russell CJ, Boyd K, Babu YS, Taylor G, Xiong X, Yan X, Portner A, Alymova IV
(2009) Antimicrob Agents Chemother 53: 3942-51
MeSH Terms: Animals, Antiviral Agents, Azides, Cell Line, Cricetinae, Female, Haplorhini, Hexuronic Acids, Humans, Mice, Parainfluenza Virus 3, Human, Sendai virus, Sulfonamides
Show Abstract · Added March 5, 2014
Human parainfluenza virus type 3 (hPIV-3) is a major respiratory tract pathogen that affects young children, but no vaccines or antiviral drugs against it have yet been developed. We developed a mouse model to evaluate the efficacies of the novel parainfluenza virus hemagglutinin-neuraminidase (HN) inhibitors BCX 2798 and BCX 2855 against a recombinant Sendai virus (rSeV) in which the fusion (F) and HN surface glycoproteins (FHN) were replaced by those of hPIV-3 [rSeV(hPIV-3FHN)]. In the prophylaxis model, 129X1/SvJ mice were infected with a 90% or 20% lethal dose of the virus and were treated intranasally for 5 days with 10 mg/kg of body weight/day of either compound starting 4 h before infection. Prophylactic treatment of the mice with either compound did not prevent their death in a 90% lethality model of rSeV(hPIV-3FHN) infection. However, it significantly reduced the lung virus titers, the amount of weight lost, and the rate of mortality in mice infected with a 20% lethal virus dose. In the therapy model, mice were infected with a nonlethal dose of the virus (100 PFU/mouse) and were treated intranasally with 1 or 10 mg/kg/day of either compound for 5 days starting at 24 or 48 h postinfection. Treatment of the mice with either compound significantly reduced the virus titer in the lungs, subsequently causing a reduction in the number of immune cells and the levels of cytokines in the bronchoalveolar lavage fluid and histopathologic changes in the airways. Our results indicate that BCX 2798 and BCX 2855 are effective inhibitors of hPIV-3 HN in our mouse model and may be promising candidates for the prophylaxis and treatment of hPIV-3 infection in humans.
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13 MeSH Terms
A RhoA-derived peptide inhibits syncytium formation induced by respiratory syncytial virus and parainfluenza virus type 3.
Pastey MK, Gower TL, Spearman PW, Crowe JE, Graham BS
(2000) Nat Med 6: 35-40
MeSH Terms: Amino Acid Sequence, Animals, Cell Fusion, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Giant Cells, Humans, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Parainfluenza Virus 3, Human, Peptide Fragments, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Vaccinia virus, rhoA GTP-Binding Protein
Show Abstract · Added August 6, 2012
The fusion glycoproteins of human respiratory syncytial virus (RSV) and human parainfluenza virus type-3 (PIV-3) mediate virus entry and syncytium formation. Interaction between the fusion protein of RSV and RhoA, a small GTPase, facilitates virus-induced syncytium formation. We show here a RhoA-derived peptide inhibits RSV and syncytium formation induced by RSV and PIV-3, both in vitro by inhibition of cell-to-cell fusion and in vivo by reduction of peak titer by 2 log10 in RSV-infected mice. These findings indicate that the interaction between these two paramyxovirus fusion proteins and RhoA is an important target for new antiviral strategies.
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16 MeSH Terms
Immune responses of infants to infection with respiratory viruses and live attenuated respiratory virus candidate vaccines.
Crowe JE
(1998) Vaccine 16: 1423-32
MeSH Terms: Child, Humans, Infant, Infant, Newborn, Influenza Vaccines, Parainfluenza Virus 3, Human, Respiratory Syncytial Virus, Human, Respiratory Tract Infections, Vaccines, Attenuated, Viral Vaccines
Show Abstract · Added August 6, 2012
Respiratory viruses such as respiratory syncytial virus (RSV), the parainfluenza viruses (PIV), and the influenza viruses cause severe lower respiratory tract diseases in infants and children throughout the world. Experimental live attenuated vaccines for each of these viruses are being developed for intranasal administration in the first weeks or months of life. A variety of promising RSV, PIV-3, and influenza virus vaccine strains have been developed by classical biological methods, evaluated extensively in preclinical and clinical studies, and shown to be attenuated and genetically stable. The ongoing clinical evaluation of these vaccine candidates, coupled with recent major advances in the ability to develop genetically engineered viruses with specified mutations, may allow the rapid development of respiratory virus strains that possess ideal levels of replicative capacity and genetic stability in vivo. A major remaining obstacle to successful immunization of infants against respiratory virus associated disease may be the relatively poor immune response of very young infants to primary virus infection. This paper reviews the immune correlates of protection against disease caused by these viruses, immune responses of infants to naturally-acquired infection, and immune responses of infants to experimental infection with candidate vaccine viruses.
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10 MeSH Terms
An update on approaches to the development of respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) vaccines.
Murphy BR, Hall SL, Kulkarni AB, Crowe JE, Collins PL, Connors M, Karron RA, Chanock RM
(1994) Virus Res 32: 13-36
MeSH Terms: Adult, Animals, Antibodies, Anti-Idiotypic, Antibodies, Viral, Clinical Trials as Topic, Humans, ISCOMs, Immunity, Maternally-Acquired, Infant, Infant, Newborn, Influenza Vaccines, Influenza, Human, Mice, Pan troglodytes, Parainfluenza Virus 3, Human, Peptide Fragments, Respiratory Syncytial Virus Infections, Respiratory Syncytial Viruses, Sigmodontinae, Vaccination, Vaccines, Attenuated, Vaccines, Synthetic, Viral Vaccines
Show Abstract · Added August 6, 2012
RSV and PIV3 are responsible for about 30% of severe viral respiratory tract disease leading to hospitalization of infants and children. For this reason, there is a need to develop vaccines effective against these viruses. Since these viruses cause severe disease in early infancy, vaccines must be effective in the presence of maternal antibody. Currently, several strategies for immunization against these viruses are being explored including peptide vaccines, subunit vaccines, vectored vaccines (e.g., vaccinia-RSV or adenovirus-RSV recombinants), and live attenuated virus vaccines. The current status of these approaches is reviewed. In addition, the immunologic basis for the disease potentiation seen in vaccinees immunized with formalin-inactivated RSV during subsequent RSV infection is reviewed. The efficacy of immunization in the presence of maternal antibody is discussed. Much progress for a RSV and PIV3 vaccine has been made and successful immunization against each of these pathogens should be achieved within this decade.
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23 MeSH Terms