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SIVsmmPBj14 induces expression of a mucosal integrin on macaque lymphocytes
S Gummuluru1, F J Novembre, B Seshi
1Department of Microbiology and Immunology, University of Rochester Medical Center, New York 14642, USA.
Abstract:
The PBj14 isolate of simian immunodeficiency virus, SIVsmmPBj14, is an acutely pathogenic lentivirus that causes severe gastrointestinal disease in macaque monkeys. The studies reported here examine the basis for the enteropathic phenotype of SIVsmmPBj14, using flow cytometric analysis of cultured macaque lymphocytes and immunohistochemical staining of tissue specimens from virus-infected macaques. The data show that enteropathic molecular clones of SIVsmmPBj14 induce expression of the alpha E beta 7 integrin, which is believed to mediate mucosal retention of T-cells, whereas molecular clones from nonenteropathic derivatives of SIVsmmPBj14 do not do so. Thus, elevated expression of alpha E beta 7 may ber responsible, at least in part, for the accumulation of abnormally large numbers of T-cells within the intestinal mucosa during acute SIVsmmPBj14 infection.
Insights
Simian immunodeficiency virus (SIVsmmPBj14) causes severe gut disease in macaques. This study links this SIV strain to increased alpha E beta 7 integrin expression, potentially explaining T-cell accumulation in the gut.
Area of Science:
- Virology
- Immunology
- Gastroenterology
Background:
- Simian immunodeficiency virus (SIVsmmPBj14) is a pathogenic lentivirus causing severe gastrointestinal disease in macaques.
- The enteropathic phenotype of SIVsmmPBj14 is not fully understood.
Purpose of the Study:
- To investigate the molecular basis for the enteropathic phenotype of SIVsmmPBj14.
- To determine the role of alpha E beta 7 integrin in SIV-induced gastrointestinal disease.
Main Methods:
- Flow cytometric analysis of cultured macaque lymphocytes.
- Immunohistochemical staining of tissue specimens from SIV-infected macaques.
Main Results:
- Enteropathic SIVsmmPBj14 molecular clones induced alpha E beta 7 integrin expression.
- Non-enteropathic SIVsmmPBj14 molecular clones did not induce alpha E beta 7 integrin expression.
- Elevated alpha E beta 7 integrin expression correlated with T-cell accumulation in the intestinal mucosa.
Conclusions:
- Elevated alpha E beta 7 integrin expression is a key factor in the enteropathic phenotype of SIVsmmPBj14.
- This mechanism contributes to the accumulation of T-cells in the intestinal mucosa during acute SIV infection.
- Understanding this pathway may inform strategies for managing lentiviral gastrointestinal diseases.