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Clinical, immunological and pathological aspects of experimental feline immunodeficiency virus (FIV) infection

del Fierro, Gloria M. (1995) Clinical, immunological and pathological aspects of experimental feline immunodeficiency virus (FIV) infection. PhD thesis, Murdoch University.

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Feline immunodeficiency virus is a recently discovered feline lentivirus which clinically resembles human HIV-1 virus inducing immune dysfunction and secondary infections in cats. FIV presence has been confirmed throughout the world in domestic, feral and zoo cat populations. Older, free-roaming, diseased male cats are at the greatest risk of acquiring the infection.

There are no specific clinical signs restricted to FIV infection. However, weight loss, recurrent fever of undetermined origin, unthriftiness, inappetence, pyrexia, lymphadenopathy, anaemia, leucopenia and myeloproliferative disease have been often associated with this infection. Localised chronic progressive infections of the mouth, oral cavity, respiratory tract, skin and external ear canals, gastrointestinal tract, neurologic and renal dysfunction as well as ocular disease have also been reported. Data in this thesis confirms that cats experimentally infected with FIV and observed for up to 77 weeks postinfection display a greater tendency for more severe infection than non-FIVinfected cats. Among the FIV-infected cats, 73% had clinical disease and 27% were asymtomatic. Fever was a feature exclusively seen in 36% of FIVinfected cats in this study.

In the same cats hematologic abnormalities include relative lymphopenia, neutropenia and leucopenia in the acute stage of infection. Transient anaemias among FIV-infected cats during the acute phase of infection was also found. No hematologic abnormalities beyond the stage of early infection equivalent to the terminal stage of naturally acquired infection were found. Mortality among FIV-infected cats was 16%, and was limited to the primary stage of infection. There was no mortality in uninfected control cats.

Whilst a final or definitive diagnosis is arrived at by virus isolation, the demonstration of FIV antibodies generally establishes a conclusive diagnosis. Throughout this study, serodiagnostic methods such as ELISA, western blot and whole blood agglutination (VetRed™FIV) methods were used. Early detection was accomplished with both ELISA and VetRed™FIV. In experimentally infected cats the sensitivities and specificities of these two methods were comparable. The western blot was not as sensitive in the early phase of infection. A comprehensive field evaluation of the newly available VetRed™FIV commercial test was undertaken which demonstrated that while it was sensitive as the ELISA test, it was not as specific. This study also confirmed the high prevalence of FIV in Western Australian cats, especially mature male cats.

At the time of necropsy, FIV was successfully isolated from the bone marrow of all infected cats, but was less frequently isolated from other lymphoid organs such as the lymph node and spleen. In addition, FIV was isolated with high frequency from the salivary gland and kidney.

Since the discovery of FIV until the present time, studies on the pathogenesis of FIV have been fragmentary. One aspect of pathogenesis, the effect of FIV on lymphoid tissue was studied in depth. Lymphadenopathy was a consistent finding, which unless lymph node weights are quantified, may be overlooked clinically and at necropsy. In this study lymph node weights of FIV infected cats were twice that of uninfected controls. A regional pattern of enlargement was also apparent, where nodes not exposed to non-specific antigens from mucosal surfaces, like popliteal lymph nodes, were unequivocally enlarged because of hyperplasia. Additionally, the lymphadenopathy was present up to 77 weeks post-infection.

Histopathologic evidence of a range of mild, moderate to severe lesions in lymphoid and non-lymphoid organs was seen in this study covering a period from 12 to 77 weeks post-infection. Gross and histopathologic lesions were divided into (1) those exclusive to FIV-infected cats, (2) those seen in both infected and uninfected cats but of a greater severity in FIV-infected cats and (3) those with equal intensity in FIV-infected and uninfected cats. The principal histopathologic alterations observed in lymphoid tissues of FIV-infected cats not previously reported at the time of this study was thymic involution, while B-cell hyperplasia of the popliteal lymph nodes and spleen occurred 2-3 times more commonly in FIV-infected cats than in controls. In non-lymphoid organs, changes were myeloid hyperplasia in the bone marrow, mild to moderate inflammation in the choroid plexus and liver, severe interstitial pneumonia, severe granulomatous ileitis and FlP-associated granulomatous inflammation in multiple organs in some cats. While the most severe lesions occurred in one cat which died acutely at 12 weeks post-inoculation, lesions in cats infected from 21-77 weeks were generally mild to moderate in nature. It is apparent from this experiment that the severity of lesions is not directly influenced by the duration of infection.

In conclusion, the outstanding features of experimentally-induced FIV-infection in non-SPF cats were mild leucopenia which encompassed a lymphopenia and neutropenia, limited to the first few weeks of infection. This was accompanied by anemia. More importantly, this study established clinical signs that were exclusive to infection and some signs that occurred with more frequency and were more severe in FIV-infected cats. Significant pathological features included lymphadenopathy, which was present in all FIV-infected cats and persisted up to 77 weeks p.i. The need for quantification to establish the presence of lymphadenopathy is emphasized. In general terms FIV infection induced a widespread B-cell hyperplasia which was not limited to lymph nodes. Accompanying this B-cell hyperplasia and not previously reported was thymic involution. Finally, with respect to the presence of FIV in particular tissues, it is apparent from this work that the preferred site for viral isolation is bone marrow, wherein virus was isolated from every infected cat in these experiments. In contrast, the frequency of isolation from lymphoid tissues such as spleen and lymph node was much less frequent. The reasons for this decreased frequency of isolation were not explored in depth. However, it does suggest that there is either less virus present in these tissues or that the rescue of virus from these tissues is more difficult. A surprising feature of the virus isolation study was the high frequency of recovery of FIV from epithelial tissues such as salivary gland and kidney. This suggests that FIV resides in cells of the bone marrow and lymphoid tissues but also in epithelial cells.

The clinicopathologic, pathologic and virologic data from the experiments described herein indicate that FIV produces a mild acute disease and remains clinically silent for a comparatively long period of time. An in depth examination of the differences between the controls and the experimentally infected cats was required in this comparatively subtle infection to detect differences between them.

Item Type: Thesis (PhD)
Murdoch Affiliation(s): School of Veterinary Studies
Notes: Note to the author: If you would like to make your thesis openly available on Murdoch University Library's Research Repository, please contact: Thank you.
Supervisor(s): Robinson, Wayne
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