Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infection in vivo is demanding, as multiple IFN subtypes with overlapping activities are produced.

Human metapneumovirus: enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged.

Cotton rats (Sigmodon hispidus) are susceptible to the recently discovered human metapneumovirus (hMPV), an agent closely related to human respiratory syncytial virus. Since certain respiratory syncytial virus vaccines can induce enhanced disease upon viral challenge, we have done similar experiments with hMPV in cotton rats. Young adult cotton rats were vaccinated with a formalin-inactivated preparation of hMPV strain C-85473, or with a mock preparation of the vaccine on day 0 and again on day 28.

A comprehensive murine model to evaluate topical vaginal microbicides: mucosal inflammation and susceptibility to genital herpes as surrogate markers of safety.

A critical gap in microbicide development is the absence of surrogate safety markers. The objective of the present study was to develop a murine model to examine the mucosal response to microbicides and to assess the functional implication of observed changes. Mice received 14 daily intravaginal doses of nonoxynol-9, PRO 2000, or placebo gel.

Interferon-inducible Mx gene expression in cotton rats: cloning, characterization, and expression during influenza viral infection.

Mx proteins belong to the superfamily of large GTPases with antiviral activity against a wide range of RNA viruses. In vivo, the expression of Mx genes is tightly regulated by the presence of type I interferons (IFNs), and their induction has been described during several viral infections. However, because of the absence of functional Mx genes in most common laboratory strains of mice, in vivo studies of the expression of these genes during viral infection have been hampered.

Age-related differences in pulmonary cytokine response to respiratory syncytial virus infection: modulation by anti-inflammatory and antiviral treatment.

Background: Respiratory syncytial virus (RSV) is the major cause of severe lower respiratory tract infection in infants and young children. Recently, RSV has also been recognized as a serious health risk in elderly individuals, but the pathogenesis of RSV infection in elderly individuals remains unknown.

Methods: Dynamics of pulmonary cytokine response (including interferon- gamma , interleukin [IL]-4, IL-10, IL-6, monocyte chemoattractant protein-1, and growth-regulated oncogene [GRO] mRNA) during acute RSV infection were investigated in young (<2 months old) and aged (>9 months old) cotton rats (Sigmodon hispidus).

The cotton rat provides a novel model to study genital herpes infection and to evaluate preventive strategies.

Prevention of genital herpes and other sexually transmitted infections (STI) is a critical health priority because of the overwhelming impact on women and infants and the epidemiological association with human immunodeficiency virus (HIV)/AIDS. Small animal models are essential for evaluating strategies for prevention or treatment of STI. Neither the murine nor the guinea pig model of genital herpes fully recapitulates human disease.

The cotton rat provides a useful small-animal model for the study of influenza virus pathogenesis.

Influenza A virus continues to cause annual epidemics. The emergence of avian viruses in the human population poses a pandemic threat, and has highlighted the need for more effective influenza vaccines and antivirals. Development of such therapeutics would be enhanced by the use of a small-animal model that is permissive for replication of human influenza virus, and for which reagents are available to dissect the host response.

Immunoprotective activity and safety of a respiratory syncytial virus vaccine: mucosal delivery of fusion glycoprotein with a CpG oligodeoxynucleotide adjuvant.

CpG oligodeoxynucleotides (ODN) were identified that stimulated immunoglobulin production and cell proliferation in cotton rat cells in vitro. Three of these ODN were used as a mucosal adjuvant in the noses of cotton rats immunized via this route with respiratory syncytial virus fusion (F) protein. The CpG ODN markedly increased the cotton rat humoral neutralizing-antibody response to respiratory syncytial virus.

A cotton rat model of human parainfluenza 3 laryngotracheitis: virus growth, pathology, and therapy.

Parainfluenza virus type 3 (PIV3) infection led to laryngotracheitis in cotton rats. Laryngeal virus titers peaked at 10(5.0)-10(6.

Age-dependent replication of respiratory syncytial virus in the cotton rat.

Despite the documented disease burden of respiratory syncytial virus (RSV) in the elderly, little is known about the underlying risk factors or pathogenesis of RSV in a geriatric population. This report describes an age-dependent change of RSV clearance in the lung and nose of the cotton rat. Six days postinfection with RSV, lung and nose viral titers were significantly higher in all older age groups as compared with 4- to 6-week old cotton rats (P < 0.

Cytokine and chemokine gene expression after primary and secondary respiratory syncytial virus infection in cotton rats.

The induction of pro- and anti-inflammatory cytokines and chemokines was studied in the lungs of cotton rats after primary or secondary infection with respiratory syncytial virus (RSV). Increases in messenger RNA (mRNA) levels of all genes analyzed were observed during the course of primary infection. In general, mRNA expression peaked between postinfection days 1 and 4 and returned to near-normal levels by day 10.

Comparison of corticosteroids for treatment of respiratory syncytial virus bronchiolitis and pneumonia in cotton rats.

Triamcinolone acetonide, methylprednisolone, and dexamethasone were each evaluated in combination with palivizumab (Synagis) for the therapy of established respiratory syncytial virus infection in the cotton rat. Triamcinolone and methylprednisolone proved to be more effective than dexamethasone in reducing lung pathology. No recurrence of viral replication or pulmonary pathology followed the cessation of therapy.

Vaccine-enhanced respiratory syncytial virus disease in cotton rats following immunization with Lot 100 or a newly prepared reference vaccine.

A formalin-inactivated respiratory syncytial virus vaccine was used to immunize infants in the mid-1960s; when these children later were naturally infected by the virus they developed markedly accentuated disease, and two died. For the present work, a new batch of vaccine was prepared using the original formula. Administration of either the old or new vaccines resulted in enhanced lesions in immunized cotton rats subsequently challenged with live virus, although administration of the vaccine reduced virus replication by 90%.