Live, attenuated simian immunodeficiency virus SIVmac-M4, with point mutations in the Env transmembrane protein intracytoplasmic domain, provides partial protection from mucosal challenge with pathogenic SIVmac251
| Autor: | Murray B. Gardner, Barbara L. Shacklett, Pierre Sonigo, David T. Wilkens, Catherine A. Cox, Karen E. S. Shaw, David C. Montefiori, Lou Adamson, Paul A. Luciw |
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| Rok vydání: | 2002 |
| Předmět: |
animal diseases
viruses Immunology Retroviridae Proteins Oncogenic Simian Acquired Immunodeficiency Syndrome Viremia CD8-Positive T-Lymphocytes medicine.disease_cause Antibodies Viral Vaccines Attenuated Microbiology Virus Immune system Neutralization Tests Virology Vaccines and Antiviral Agents medicine Animals Point Mutation Attenuated vaccine biology Vaccination Mouth Mucosa SAIDS Vaccines virus diseases Gene Products env Simian immunodeficiency virus Viral Load medicine.disease biology.organism_classification Macaca mulatta Simian AIDS Animals Newborn Insect Science Lentivirus Simian Immunodeficiency Virus Viral load Viral Fusion Proteins |
| Zdroj: | Journal of virology. 76(22) |
| ISSN: | 0022-538X |
| Popis: | Attenuated molecular clones of simian immunodeficiency virus (SIVmac) are important tools for studying the correlates of protective immunity to lentivirus infection in nonhuman primates. The most highly attenuated SIVmac mutants fail to induce disease but also fail to induce immune responses capable of protecting macaques from challenge with pathogenic virus. We recently described a novel attenuated virus, SIVmac-M4, containing multiple mutations in the transmembrane protein (TM) intracytoplasmic domain. This domain has been implicated in viral assembly, infectivity, and cytopathogenicity. Whereas parental SIVmac239-Nef+induced persistent viremia and simian AIDS in rhesus macaques, SIVmac-M4 induced transient viremia in juvenile and neonatal macaques, with no disease for at least 1 year postinfection. In this vaccine study, 8 macaques that were infected as juveniles (n= 4) or neonates (n= 4) with SIVmac-M4 were challenged with pathogenic SIVmac251 administered through oral mucosa. At 1 year postchallenge, six of the eight macaques had low to undetectable plasma viremia levels. Assays of cell-mediated immune responses to SIVmac Gag, Pol, Env, and Nef revealed that all animals developed strong CD8+T-cell responses to Gag after challenge but not before. Unvaccinated control animals challenged with SIVmac251 developed persistent viremia, had significantly weaker SIV-specific T-cell responses, and developed AIDS-related symptoms. These findings demonstrate that SIVmac-M4, which contains a full-length Nef coding region and multiple point mutations in the TM, can provide substantial protection from mucosal challenge with pathogenic SIVmac251. |
| Databáze: | OpenAIRE |
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