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Published on: August 15, 2012
Productive infection of human peripheral blood mononuclear cells by feline immunodeficiency virus: implications for
1Department of Clinical Neurosciences and Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Insights
Feline immunodeficiency virus (FIV) can infect human cells, utilizing the CCR3 receptor. This FIV infection of human cells leads to increased cell death, highlighting strain specificity for potential gene therapy applications.
Area of Science:
- Virology
- Immunology
- Gene Therapy
Background:
- Feline immunodeficiency virus (FIV) is a lentivirus known to cause immune suppression and neurological issues in cats.
- FIV, similar to primate lentiviruses, uses the chemokine receptor CXCR4 for infection.
- Previous studies indicated FIV gene expression in immortalized human cell lines.
Purpose of the Study:
- To investigate the extent and mechanisms of FIV infection in primary and immortalized human cell lines.
- To compare the infectivity of two distinct FIV strains (V1CSF and Petaluma) in human cells.
- To assess the potential of FIV as a vector for gene therapy.
Main Methods:
- Cell-free infection of human peripheral blood mononuclear cells (PBMC) and macrophages with FIV strains V1CSF and Petaluma.
- Detection of FIV genome using PCR.
- Flow cytometry analysis to identify infected cells and receptor usage.
- Measurement of reverse transcriptase levels and viral titers.
- Assessment of cell viability in infected cultures.
Main Results:
- FIV genome was detected in human PBMC and macrophages post-infection.
- Antibodies targeting the CCR3 chemokine receptor significantly inhibited FIV infection in human PBMC, more so than CXCR4 or CCR5.
- Increased reverse transcriptase levels and viral titers were observed in infected human PBMC.
- FIV infection led to significantly elevated cell death in human PBMC compared to controls.
Conclusions:
- Feline immunodeficiency virus (FIV) can productively infect primary human cell lines.
- The CCR3 chemokine receptor plays a crucial role in FIV infection of human cells.
- Viral strain specificity is a critical consideration for developing FIV-based vectors for gene therapy.
Abstract:
Feline immunodeficiency virus (FIV) is a lentivirus causing immune suppression and neurological disease in cats. Like primate lentiviruses, FIV utilizes the chemokine receptor CXCR4 for infection. In addition, FIV gene expression has been demonstrated in immortalized human cell lines. To investigate the extent and mechanism by which FIV infected primary and immortalized human cell lines, we compared the infectivity of two FIV strains, V1CSF and Petaluma, after cell-free infection. FIV genome was detected in infected human peripheral blood mononuclear cells (PBMC) and macrophages at 21 and 14 days postinfection, respectively. Flow cytometry analysis of FIV-infected human PBMC indicated that antibodies to FIV p24 recognized 12% of the cells. Antibodies binding the CCR3 chemokine receptor maximally inhibited infection of human PBMC by both FIV strains compared to antibodies to CXCR4 or CCR5. Reverse transcriptase levels increased in FIV-infected human PBMC, with detection of viral titers of 10(1.3) to 10(2.1) 50% tissue culture infective doses/10(6) cells depending on the FIV strain examined. Cell death in human PBMC infected with either FIV strain was significantly elevated relative to uninfected control cultures. These findings indicate that FIV can productively infect primary human cell lines and that viral strain specificity should be considered in the development of an FIV vector for gene therapy.
