Expanded tissue targets for foamy virus replication with simian immunodeficiency virus-induced immunosuppression

Area of Science:

• Virology
• Immunology
• Primate models

Background:

• Foamy viruses (FV) are ancient retroviruses with lifelong, nonpathogenic infections in nonhuman primates, typically transmitted via saliva.
• FV exhibit rapid in vitro cytopathicity, contrasting with in vivo persistence, suggesting host immune control.
• Understanding FV tissue tropism and host defense mechanisms is crucial, especially in the context of immunosuppression.

Purpose of the Study:

• To investigate the tissue-specific replication of FV in rhesus macaques (RM).
• To determine how simian immunodeficiency virus (SIV)-induced immunosuppression affects FV tissue distribution.
• To elucidate the host immune response and environmental factors influencing FV tropism.

Main Methods:

• Quantification of viral RNA in various tissues of healthy and SIV-infected RM.
• Comparison of FV levels in oral tissues versus the small intestine and other examined tissues.
• Analysis of FV tropism in relation to CD4+ T-cell depletion and jejunal microenvironment.

Main Results:

• Immunocompetent RM consistently showed high FV RNA levels in oral tissues, but not the small intestine.
• SIV-infected RM exhibited abundant FV transcripts in the small intestine, a site of SIV-induced CD4+ T-cell depletion.
• A trend towards lower FV RNA levels was observed in the oropharyngeal tissues of SIV-infected animals.

Conclusions:

• FV replication expands to the small intestine in SIV-infected RM, independent of other CD4+ T-cell-depleted tissues.
• Dysregulation of the jejunal microenvironment post-SIV infection likely drives the expanded tissue tropism of FV.
• Host factors beyond T-cell depletion significantly influence FV replication patterns during immunosuppression.