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In vivo monocyte tropism of pathogenic feline immunodeficiency viruses
S W Dow1, C K Mathiason, E A Hoover
1Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
Abstract:
Virus-infected monocytes rarely are detected in the bloodstreams of animals or people infected with immunodeficiency-inducing lentiviruses, yet tissue macrophages are thought to be a major reservoir of virus-infected cells in vivo. We have identified feline immunodeficiency virus (FIV) clinical isolates that are pathogenic in cats and readily transmitted vertically. We report here that five of these FIV isolates are highly monocytotropic in vivo. However, while FIV-infected monocytes were numerous in the blood of experimentally infected cats, viral antigen was not detectable in freshly isolated cells. Only after a short-term (at least 12-h) in vitro monocyte culture were FIV antigens detectable (by immunocytochemical analysis or enzyme-linked immunosorbent assay). In vitro experiments suggested that monocyte adherence provided an important trigger for virus antigen expression. In the blood of cats infected with a prototype monocytotropic isolate (FIV subtype B strain 2542), infected monocytes appeared within 2 weeks, correlating with high blood mononuclear-cell-associated viral titers and CD4 cell depletion. By contrast, infected monocytes could not be detected in the blood of cats infected with a less pathogenic FIV strain (FIV subtype A strain Petaluma). We concluded that some strains of FIV are monocytotropic in vivo. Moreover, this property may relate to virus virulence, vertical transmission, and infection of tissue macrophages.
Insights
Some feline immunodeficiency virus (FIV) strains infect monocytes in cats, but viral antigens are only detectable after cell culture. This monocytotropism may influence FIV virulence and transmission.
Area of Science:
- Immunology
- Virology
- Veterinary Medicine
Background:
- Monocytes are crucial immune cells, yet virus-infected monocytes are rarely detected in lentivirus infections.
- Tissue macrophages are considered a primary reservoir for immunodeficiency-inducing lentiviruses in vivo.
- Feline immunodeficiency virus (FIV) causes immune deficiency in cats and can be transmitted vertically.
Purpose of the Study:
- To investigate the in vivo tropism of pathogenic FIV clinical isolates in cats.
- To determine if FIV infects monocytes and if this correlates with disease progression.
- To understand the role of monocyte culture conditions in FIV antigen detection.
Main Methods:
- Experimental infection of cats with pathogenic and less pathogenic FIV strains.
- Isolation and culture of feline monocytes from infected cats.
- Detection of FIV antigens using immunocytochemical analysis and enzyme-linked immunosorbent assay (ELISA).
- Monitoring of viral load and CD4 cell counts in infected cats.
Main Results:
- Five pathogenic FIV isolates demonstrated significant monocytotropism in vivo.
- FIV-infected monocytes were abundant in the blood of experimentally infected cats.
- Viral antigens were undetectable in freshly isolated monocytes but became detectable after 12-hour in vitro culture.
- Monocyte adherence in vitro appeared to trigger FIV antigen expression.
- Monocytotropic FIV infection correlated with high viral titers and CD4 cell depletion.
- Less pathogenic FIV strains did not show detectable infected monocytes in blood.
Conclusions:
- Certain FIV strains exhibit monocytotropism in vivo.
- Monocyte infection and antigen expression are influenced by in vitro culture conditions, particularly adherence.
- FIV monocytotropism may be linked to virus virulence, vertical transmission, and the establishment of infection in tissue macrophages.