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Objective: To determine the potential mechanisms for disease potentiation where feline immunodeficiency virus (FIV) infection of persistently feline leukemia virus (FeLV)-infected cats results in more severe FIV disease and increased mortality than FIV infection of specific pathogen-free cats., Design and Methods: To determine whether pseudotype formation resulting in expanded cell tropism may be an important mechanism, cellular targets and tissue distribution of FIV and FeLV were determined by in situ hybridization and/or immunohistochemistry. To determine whether FeLV can transactivate the FIV long terminal repeat (LTR) resulting in increased FIV expression, in vitro transient expression assays were performed. To examine whether persistent FeLV infection can cause the deletion of a suppressive T-lymphocyte population, peripheral blood mononuclear cell (PBMC) cultures from persistently FeLV-infected cats were infected with FIV and monitored for FIV antigen levels., Results: Macrophages were the predominant target of FIV infection and were disseminated in a similar pattern in lymphoid and nonlymphoid tissues of both FIV-infected and FeLV/FIV-coinfected cats. FeLV-infected cells expressing FIV RNA were not present. Significant transactivation of the FIV LTR in FeLV-infected cells was not demonstrated. FIV antigen production was similar upon in vitro infection of PBMC from FeLV-infected and uninfected cats., Conclusions: Neither direct virus/virus interactions, such as FeLV/FIV pseudotype formation or transactivation of the FIV LTR in FeLV-infected cells, nor deletion of a regulatory cell subset from the blood of FeLV-infected cats, was found to be the mechanism of disease potentiation.

The objective of this study was to identify cellular and organ targets of acute feline immunodeficiency virus (FIV) infection in vivo. Tissues of FIV-infected cats were studied at eight time points during the first 3 months after experimental infection. FIV nucleic acids were first detected by in situ hybridization 21 days after infection, approximately 1.5 weeks after lymph node enlargement was first observed and 3 weeks before the primary acute flu-like illness. The majority of FIV-infected cells were present in lymphoid organs, though low numbers of infected cells were noted in nonlymphoid organs as well. Germinal centers harbored many of the FIV-infected cells within lymphoid tissues. The thymic cortex was also a major site of early infection. Combined in situ hybridization and immunohistochemistry revealed that T lymphocytes were the primary target of early FIV infection in tissues of cats before the onset of clinical signs of acute illness. An unidentified population of mononuclear cells and a few macrophages were also infected. During the ensuing acute flu-like illness, the proportion of FIV-infected macrophages in tissues increased dramatically. This early shift in the predominant cellular localization of FIV from T lymphocytes to macrophages may be important for establishing viral persistence.