Altered tryptophan metabolism in FIV-positive cats

BACKGROUND: Feline immunodeficiency virus (FIV) is analogous to human immunodeficiency virus, the causative agent of human acquired immunodeficiency syndrome (AIDS). In AIDS patients, a progressive reduction in serum tryptophan concentration occurs because of activation of an inducible tryptophan degradation pathway mediated by elevated lamda-interferon production. HYPOTHESIS: Cats infected with FIV have increased tryptophan catabolism evidenced by reduced circulating concentrations of tryptophan and increased concentrations of the tryptophan catabolite kynurenine. ANIMALS: Convenience sample of 235 cats submitted for diagnostic FIV serology (115 FIV-negative and 120 FIV-positive cats). METHODS: Retrospective, cross-sectional study. Serum was assayed for tryptophan and kynurenine using a high performance liquid chromatography assay with fluorescence and ultraviolet detection, respectively. RESULTS: Tryptophan and kynurenine concentrations were log-normally distributed. Geometric mean concentrations were: tryptophan: FIV-positive 30.6 microM (95% CI: 26.8 34.8 microM), FIV-negative 48.9 [microM (95% CI: 43.6-54.9 microM) (P < .001); kynurenine: FIV-positive 22.7 microM (95% CI: 25.5-10.9 microM), FIV-negative 9.9 microM (95% CI: 20.3-9.03 microM) (P < .001). The ratio of kynurenine to tryptophan was: FIV-positive 4.93 (95% CI: 5.62-4.32), FIV-negative 1.34 (95% CI: 1.53 1.17) (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum tryptophan concentration was significantly lower and serum kynurenine concentration was significantly higher in FIV-positive cats. The kynurenine: tryptophan ratio was >3-fold higher in FIV-positive animals, indicating increased tryptophan catabolism in this group. Dietary or pharmacologic intervention to support serum tryptophan concentrations has been shown to be clinically useful in humans with AIDS and might be applicable to cats with FIV infection.     

Epidemiologic observations on feline immunodeficiency virus and Toxoplasma gondii coinfection in cats in Baltimore, Md

Five hundred eighty-five serum samples obtained between 1980 and 1981 from a diverse population of cats were tested by use of an indirect immunoperoxidase assay for antibodies to feline immunodeficiency virus (FIV). Results of 14 of the samples were positive (prevalence, 2.4%). The FIV-positive cats were markedly older than the overall population and frequently were coinfected (57%) with Toxoplasma gondii. The Toxoplasma titers of the FIV-positive cats were significantly (P less than 0.03) higher than those of the FIV-negative cats. The FIV-positive cats were not coinfected with FeLV. Our findings suggested that FIV-associated immunosuppression may be a factor in active Toxoplasma infection in adult cats.     

Analysis of leucocytes and lymphocyte subsets in cats with naturally-occurring cryptococcosis but differing feline immunodeficiency virus status

SUMMARY: Although cryptococcosis is a well-characterised disease of cats, the factors predisposing individuals to infection are unknown. As an indication of the immune status of an individual, lymphocyte subsets can be analysed. Reference ranges for feline lymphocyte subsets (Pan T+, CD4+, CDS+ and B cells) were established using a rapid whole blood technique and flow cytometry. There were no effects of age or sex on lymphocyte subset values. The numbers of circulating leucocytes and lymphocyte subsets were determined in FIV-positive and FIV-negative cats with cryptococcosis and compared with a group of healthy control cats.
There were only minor differences in the numbers of lymphocyte subsets among the subgroups of cats examined in the study and the predisposition to cryptococcosis in cats could not be explained by deficiencies in lymphocyte subsets. There was a tendency for FIV-negative cats with cryptococcosis to have reduced numbers of circulating CD4+ cells and lower CD4:CD8 ratios compared with normal cats, although the interpretation of this finding was complicated by the wide reference range for normal cats. The extent to which this is the cause of the fungal infection was not determined.
The only difference in leucocyte or lymphocytes subset values between FIV-negative cats with cryptococcosis and FIV-positive cats with cryptococcosis was that the CD4+ percentage was lower in the FIV-positive cats. The absolute CD4+ count was similar however, in FIV-positive and FIV-negative cryptococcosis cases. On the basis of this and other available information, the categorisation of cryptococcosis as a disease defining the AIDS phase of FIV infection may be incorrect.     

Vaccination of cats experimentally infected with feline immunodeficiency virus, using a recombinant feline leukemia virus vaccine.

A group of 15 cats experimentally infected with a Swiss isolate of feline immunodeficiency virus (FIV) and a group of 15 FIV-negative control cats were inoculated with an FeLV vaccine containing recombinant FeLV-envelope. High ELISA antibody titer developed after vaccination in FIV-positive and FIV-negative cats. Vaccinated and nonvaccinated controls were later challenge exposed by intraperitoneal administration of virulent FeLV subtype A (Glasgow). Although 12 of 12 nonvaccinated controls became infected with FeLV (10 persistently, 2 transiently), only 1 of 18 vaccinated (9 FIV positive, 9 FIV negative) cats had persistent and 2 of 18 had transient viremia. From these data and other observations, 2 conclusions were drawn: In the early phase of FIV infection, the immune system is not depressed appreciably, and therefore, cats may be successfully immunized; a recombinant FeLV vaccine was efficacious in protecting cats against intraperitoneal challenge exposure with FeLV.     

Feline leukaemia virus (FeLV) and feline immunodeficiency virus infections in cats in the Pisa district of Tuscany, and attempts to control FeLV infection in a colony of domestic cats by vaccination

The seroprevalence of feline immunodeficiency virus (FIV) in 203 apparently healthy domestic cats living in the district of Pisa, central Italy, was 11.3 per cent, and the prevalence of feline leukaemia virus (FeLV) was 8.4 per cent. The prevalence of FIV depended significantly on the lifestyle and age of the cats; cats living outdoors were more likely to be FIV-positive than cats living indoors, and the proportion of FIV-positive cats increased with age. In contrast, there was no significant relationship between these variables and the prevalence of FeLV. There was no significant relationship between the cats' seropositivity for FIV and FeLV. The results of a five-year field study to control FeLV infection by vaccination in a colony of 30 domestic adult cats naturally exposed to the infection suggest that the vaccination was effective in FIV-negative cats, but failed to protect FIV-positive cats against FeLV.     

Adenosine deaminase activity in cats infected with feline immunodeficiency virus

Adenosine deaminase (ADA), an enzyme involved in purine metabolism, has been shown to be of clinical importance in several diseases in humans. To investigate whether ADA is of any clinical significance in cats, plasma adenosine deaminase (P-ADA) and T cell adenosine deaminase (T-ADA) activities were measured in feline immunodeficiency virus (FIV) negative and positive cats. The AIDS-related complex (ARC) group showed a significant elevation in P-ADA activity compared to the asymptomatic carrier (AC), and FIV-negative groups (P<0.005). T-ADA activity was significantly elevated in FIV-positive cats compared to the FIV-negative group (P<0.05) and this elevation was attributed to the increase in the ARC group (P<0.01). A correlation was found between P-ADA and T-ADA activities in the FIV-negative group. T-ADA activity and CD4(+)cell number showed a strong negative correlation in FIV-positive cats (P<0.0005). CD4(+) cell numbers were significantly reduced in the ARC group compared to the healthy controls (P<0.005). Our results showed that T-ADA is increased in FIV-positive cats during the ARC stage. These results also suggest that ADA may be an indicator of T cell activation in the ARC stage of FIV infection.     

Prevalence of feline immunodeficiency virus infection in domesticated and feral cats in eastern Australia

Serum samples from 340 pet cats presented to three inner city clinics in Sydney Australia, 68 feral cats from two separate colonies in Sydney, and 329 cattery-confined pedigree and domestic cats in eastern Australia, were collected over a 2-year period and tested for antibodies directed against feline immunodeficiency virus (FIV) using immunomigration (Agen FIV Rapid Immunomigration test) and enzyme-linked immunosorbent assay methods (Snap Combo feline leukaemia virus antigen/FIV antibody test kit, IDEXX Laboratories). Western blot analysis was performed on samples in which there was discrepancy between the results. Information regarding breed, age, gender, housing arrangement and health status were recorded for all pet and cattery-confined cats, while the estimated age and current physical condition were recorded for feral cats. The FIV prevalence in the two feral cat populations was 21% and 25%. The majority of FIV-positive cats were male (60-80%). The FIV prevalence in cattery-confined cats was nil. The prevalence of FIV in the pet cat sample population was 8% (27/340) with almost equal prevalence in 'healthy' (13/170) and 'systemically unwell' (14/170) cats. The age of FIV-positive pet cats ranged from 3 to 19 years; all FIV-positive cats were domestic shorthairs with outside access. The median age of FIV-positive pet cats (11 years) was significantly greater than the median age of FIV-negative pet cats (7.5 years: P<0.05). The prevalence of FIV infection in male pet cats (21/172; 12%) was three times that in female pet cats (6/168; 4%; P<0.05). With over 80% of this pet cat population given outside access and continued FIV infection present in the feral population, this study highlights the need to develop rapid, accurate and cost-effective diagnostic methods that are not subject to false positives created by concurrent vaccination against FIV. This is especially important in re-homing stray cats within animal shelters and monitoring the efficacy of the new vaccine, which has not been challenged against Australian strains. The absence of FIV within cattery-confined cats highlights the value in routine screening and indoor lifestyles. This study provides cogent baseline FIV prevalences in three cat subpopulations which can be used for appraising potential disease associations with FIV in Australia.     

The variability of serological and molecular diagnosis of feline immunodeficiency virus infection

Diagnosis of feline immunodeficiency virus (FIV) infection by polymerase chain reaction (PCR) has recently become available, but little is known about the performance of this assay. The purpose of this study was to determine the sensitivity and specificity of PCR diagnosis of FIV infection. Replicate aliquots of blood samples from cats identified as FIV positive or negative by 2 previous enzyme-linked immunosorbent assay (ELISA) results, and from clinically healthy dogs, were submitted to different laboratories for FIV serologic diagnosis and PCR. The PCR products obtained in 1 laboratory were sequenced to determine the FIV subtype. The PCR assays correctly identified 100%, 80%, and 50% of the FIV-positive samples, and 100%, 90%, and 70% of FIV-negative samples. Each dog sample was reported as FIV PCR positive at least once, and FIV subtypes A, B, and C were identified. It was concluded that PCR tests currently available for FIV infection are unreliable, with highly variable sensitivity and specificity.     

No evidence of vertical transmission of naturally acquired feline immunodeficiency virus infection.

A naturally occurring feline immunodeficiency virus (FIV) infection in a closed breeding colony of cats, was studied for a period of 9 months. The colony consisted of 25 adult cats, of which six proved to be infected with FIV as judged by serological examination and virus isolation. In all, 48 kittens were monitored for levels of antibodies against FIV during their first 6 months of life. All the kittens (n = 30) born of FIV-infected queens showed maternal antibodies against FIV, although these declined to undetectable levels by the age of 5 months. Antibodies against FIV were not shown in any of 18 kittens born of FIV-negative queens. An attempt to isolate the virus from 12 kittens between 2 and 6 weeks of age did not succeed. None of the cats in the colony seroconverted during the observation period. In conclusion, neither vertical nor horizontal transmission of FIV infection were demonstrated in the colony during the 9-month investigation period.     

Constitutive expression of types 1 and 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats

Evidence suggests that feline immunodeficiency virus (FIV), causes pulmonary immunodeficiency. The overall objective of this study was to explore FIV-induced alterations in cell counts and cytokine gene expression in the pulmonary compartment during the acute stage infection. Bronchoalveolar lavage (BAL) cells were collected from FIV-infected and control cats at 0, 4, 10, and 16 weeks post-FIV infection for phenotype and cytokine analysis. The major change in BAL cellular populations following FIV-infection was the development of a neutrophilia. Total BAL cell counts and relative numbers of alveolar macrophages (AM), eosinophils, and lymphocytes remained similar in both groups. The RT-qcPCR analyses of AM purified from BAL showed constitutive expression of TNFalpha, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFalpha and IL6 bioactive protein secretion showed a similar response. In contrast, IFNgamma expression increased progressively with time after infection and paralleled a progressive increase in FIV-gag mRNA in AM. The IL12 p40 expression also differed from the other cytokines in that there was a progressive decrease in the number of cats with AM IL12 expression following FIV infection. Infection of AM in vitro with FIV also caused an increase in TNFalpha and IL6 mRNA and bioactive protein suggesting that the increased cytokine response by AM following infection of cats with FIV is an intrinsic characteristic of FIV-infected AM. In summary, pulmonary immune changes seen in FIV-infected cats are similar to those seen in HIV-infected human patients.     

Vaccination against the feline immunodeficiency virus: the road not taken

Natural infection of domestic cats by the feline immunodeficiency virus (FIV) causes acquired immunodeficiency syndrome (AIDS). FIV is genetically related to human immunodeficiency virus (HIV), and the clinical and biological features of infections caused by feline and human viruses in their respective hosts are highly analogous. Although the obstacles to vaccinating against FIV and HIV would seem to be of comparable difficulty, a licensed vaccine against feline AIDS is already in widespread use in several countries. While this seemingly major advance in prevention of AIDS would appear to be highly instructive for HIV vaccine development, its message has not been heeded by investigators in the HIV field. This review endeavours to relate what has been learned about vaccination against feline AIDS, and to suggest what this may mean for HIV vaccine development.     

Long-term impact on a closed household of pet cats of natural infection with feline coronavirus, feline leukaemia virus and feline immunodeficiency virus

A closed household of 26 cats in which feline coronavirus (FCoV), feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) were endemic was observed for 10 years. Each cat was seropositive for FCoV on at least one occasion and the infection was maintained by reinfection. After 10 years, three of six surviving cats were still seropositive. Only one cat, which was also infected with FIV, developed feline infectious peritonitis (FIP). Rising anti-FCoV antibody titres did not indicate that the cat would develop FIP. The FeLV infection was self-limiting because all seven of the initially viraemic cats died within five years and the remainder were immune. However, FeLV had the greatest impact on mortality. Nine cats were initially FIV-positive and six more cats became infected during the course of the study, without evidence of having been bitten. The FIV infection did not adversely affect the cats' life expectancy.     

Prevalence and risk factors for hemoplasmas in domestic cats naturally infected with feline immunodeficiency virus and/or feline leukemia virus in Rio de Janeiro--Brazil

The aim of this study was to determine the prevalence and risk factors for Mycoplasma haemofelis (Mhf) and 'Candidatus Mycoplasma haemominutum' (Mhm) infections in domestic cats tested for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Based on serological testing, cats were grouped as i) FIV-positive (n=25); ii) FeLV-positive (n=39); iii) FIV/FeLV-positive (n=8); and iv) FIV/FeLV-negative (n=77). Complete blood counts were followed by DNA extraction, species-specific polymerase chain reaction (16S rRNA gene) for Mhf and Mhm and Southern blotting for all animals. Mhf DNA was found in 4.0, 2.6, 12.5 and 7.8% of the cats from groups i, ii, iii and iv, respectively, while 32, 5.1, 50 and 5.2% of these animals had an Mhm infection. Cats with FIV (OR=4.25, P=0.009) and both FIV and FeLV (OR=7.56, P=0.014) were at greater risk of being hemoplasma infected than retroviral-negative cats, mainly due to Mhm infection (OR=8.59, P=0.001 and OR=18.25, P=0.001, respectively). Among pure-breed cats, FIV-positive status was associated with hemoplasma infection (OR 45.0, P=0.001).     

Altered mitogen response of peripheral blood lymphocytes in different stages of feline immunodeficiency virus infection

To elucidate relationship between disease progress and immunologic alteration in feline immunodeficiency virus (FIV) infection, we classified naturally infected cats into clinical stage groups using the working criteria modified from those for human immunodeficiency virus (HIV) infection. Among the five distinct stages described for HIV infection, the three phases; asymptomatic carrier (AC), AIDS related complex (ARC), and acquired immunodeficiency syndrome (AIDS), were evaluated for concanavalin A (Con A)-induced lymphocyte blastogenic activities by using glucose consumption assay. There was a significant decrease of lymphocyte response in AC phase. The loss of response became marked as the disease progressed to ARC and AIDS, with an almost complete loss of mitogen response in AIDS phase. In addition to the loss of a lymphocyte function, AIDS in FIV infection was characterized by marked emaciation, anemia or pancytopenia, and postmortem evidences of opportunistic infections and lymphoid depletion.     

Serological survey of Toxoplasma gondii,feline immunodeficiency virus and feline leukaemia virus in urban stray cats in Belgium

Three hundred and forty-six serum samples taken between 1998 and 2000 from urban stray cats in the city of Ghent were tested for antibodies to Toxoplasma gondii and feline immunodeficiency virus (FIV), and antigens of feline leukemia virus (FeLV). Of these 346 samples, 243 (70.2 per cent) were seropositive for Tgondii. Thirty-nine cats (11.3 per cent) had antibodies against FIV and 13 (3.8 per cent) had circulating antigens of FeLV. Fewer of the female cats had FIV and heavier cats had a higher seroprevalence of FIV. Exact logistic regression showed that cats that were infected with FIV were more likely to be infected with T gondii (P = 0.04), and the cats with FIV had a higher titre of Tgondii antibodies than FIV-negative animals. However, FeLV was not associated with either T gondii or FIV.     

Feline immunodeficiency virus: a brief review.

Feline immunodeficiency virus (FIV), previously known as feline T-lymphotropic lentivirus (FTLV), was first described by Pedersen et al. (1987) who isolated the virus from cats with a variety of clinical signs suggestive of immunodeficiency. Since then FIV has become one of the most studied feline viruses, not least because of its similarity to human immunodeficiency viruses (HIV) which cause acquired immunodeficiency syndrome (AIDS) in man.     

Ability of CD8+ T cell anti-feline immunodeficiency virus (FIV) activity and FIV proviral DNA load in mononuclear cells in FIV-infected cats

We investigated the relationship between CD8+ T cell anti-feline immunodeficiency virus (FIV) activity and FIV proviral DNA load integrated in mononuclear cells. The anti-FIV activity and the proviral DNA load were correlated, and the number of proviral DNA copies was high in cats with decreased anti-FIV activity. Particularly, no anti-FIV activity was detected in the cats staged as having an acquired immunodeficiency syndrome (AIDS)-related complex or AIDS, and the number of proviral DNA copies was obviously increased compared to those in the cats in the asymptomatic stage. These results suggest that decreased anti-FIV activity destroys the control of in vivo FIV replication, which leads to an increased proviral DNA load with the progression of the clinical stage of disease.     

FIV vaccine development and its importance to veterinary and human medicine: a review FIV vaccine 2002 update and review

Feline immunodeficiency virus (FIV) is a natural infection of domestic cats that results in acquired immunodeficiency syndrome resembling human immunodeficiency virus (HIV) infection in humans. The worldwide prevalence of FIV infection in domestic cats has been reported to range from 1 to 28%. Hence, an effective FIV vaccine will have an important impact on veterinary medicine in addition to being used as a small animal AIDS model for humans. Since the discovery of FIV reported in 1987, FIV vaccine research has pursued both molecular and conventional vaccine approaches toward the development of a commercial product. Published FIV vaccine trial results from 1998 to the present have been compiled to update the veterinary clinical and research communities on the immunologic and experimental efficacy status of these vaccines. A brief report is included on the outcome of the 10 years of collaborative work between industry and academia which led to recent USDA approval of the first animal lentivirus vaccine, the dual-subtype FIV vaccine. The immunogenicity and efficacy of the experimental prototype, dual-subtype FIV vaccine and the efficacy of the currently approved commercial, dual-subtype FIV vaccine (Fel-O-Vax FIV) are discussed. Potential cross-reactivity complications between commercial FIV diagnostic tests, Idexx Snap Combo Test and Western blot assays, and sera from previously vaccinated cats are also discussed. Finally, recommendations are made for unbiased critical testing of new FIV vaccines, the currently USDA approved vaccine, and future vaccines in development.     

Hemostatic Disorders in Feline Immunodeficiency Virus-Seropositive Cats

The hemostatic function of 40 feline immunodeficiency virus (FlV) seropositive and 8 FIV and feline leukemia virus (FeLV) seropositive cats was evaluated and compared with reference values from 30 clinically healthy cats. The FIVpositive cats were divided into 3 groups: group I included asymptomatic carriers; group II comprised sick FIV-infected cats with illnesses not likely to influence the hemostatic system; and group III included FIV-positive cats with diseases potentially associated with coagulopathies. Platelet counts in FIV/FeLV-infected cats were significantly lower than in healthy cats (P < .003), whereas the differences in the 3 groups of FIV-positive cats were variable (group I, P= .009; II, P= .05; III, P= .09). Thrombocytopenia (< 145,000 platelets/μL) was present in 4 FIV-positive and 3 FIV/FeLV-positive cats. Platelet aggregation induced by collagen (0.5 and 0.25 μg/mL), adenosine diphosphate (ADP) (1 and 0.6 μmol/L), and thrombin (0.4 and 0.25 IU/mL) was not significantly different from that of healthy cats. The plasma coagulation system was evaluated by measuring one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration, coagulation factor assays, fibrinogen and fibrin degradation products (FDP), and plasma exchange test. The OSPT was similar in FlV-seropositive cats and in the healthy control group. Cats with FIV infection, however, had markedly shorter clotting times than healthy cats when using a modified test system (P < .05). In all groups of FIV-infected cats and in those with FIV/FeLV infection, APTT measured with 2 different commercially available tests, and a modified plasma assay was markedly prolonged compared with healthy cats (APTT1 and 2:3 modification: P < .01; APTT2: P < .05 except group III). In 22 of 40 cats with FIV and in 5 of 8 cats with FIV/FeLV infection, plasma samples were beyond the reference range. The thrombin time was also significantly prolonged in cats with FIV and FIV/FeLV infection (P < .01); values in 17 of 40 FIV-positive cats were above reference range. The mean fibrinogen concentration of cats with FIV and FIV/FeLV infection was higher than in the healthy control group (P < .001). Factor VIII activity of 4 cats with FIV infection was 1.5 times higher than that of healthy cats. Factor XII activity of 3 cats from a group of 20 cats with prolonged APTT was between 20% and 35%. Factor IX and XI activities ranged between 70% and 120%. The markedly prolonged APTT in 2 FIV-positive cats could be shortened considerably in a plasma exchange test using 20% feline pooled plasma. The alterations in the coagulogram of FIV-seropositive cats were not related to a clinical stage or concurrent diseases. A definite explanation of the distinct disorder within the intrinsic plasma coagulation system in FIV-infected cats was not found.