Improved neurocognitive performance in FIV infected cats following treatment with the p75 neurotrophin receptor ligand LM11A-31.

HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective treatment options. Neurotrophin based therapies have excellent potential to stabilize and repair the nervous system. A novel non-peptide ligand, LM11A-31, that targets the p75 neurotrophin receptor (p75NTR) has been identified as a small bioavailable molecule capable of strong neuroprotection with minimal side effects. To evaluate the neuroprotective effects of LM11A-31 in a natural infection model, we treated cats chronically infected with feline immunodeficiency virus (FIV) with 13 mg/kg LM11A-31 twice daily over a period of 10 weeks and assessed effects on cognitive functions, open field behaviors, activity, sensory thresholds, plasma FIV, cerebrospinal fluid (CSF) FIV, peripheral blood mononuclear cell provirus, CD4 and CD8 cell counts and general physiology. Between 12 and 18 months post-inoculation, cats began to show signs of neural dysfunction in T maze testing and novel object recognition, which were prevented by LM11A-31 treatment. Anxiety-like behavior was reduced in the open field and no changes were seen in sensory thresholds. Systemic FIV titers were unaffected but treated cats exhibited a log drop in CSF FIV titers. No significant adverse effects were observed under all conditions. The data indicate that LM11A-31 is likely to be a potent adjunctive treatment for the control of neurodegeneration in HIV infected individuals.

Concomitant feline immunodeficiency virus (FIV) and Mycoplasma haemofelis in a barn cat.

A 5-year-old male barn cat was presented with lethargy and excessive bleeding following castration. The patient developed hemolytic anemia and diagnostic tests revealed infection with feline immunodeficiency virus and Mycoplasma haemofelis. This case serves as a reminder of the importance of testing for infectious diseases and educating owners on feline infectious disease prevention and management.

Présence concomitante du virus de l'immunodéficience féline (FIV) et de Mycoplasma hæmofelis chez un chat de grange. Un chat de grange mâle âgé de 5 ans a été présenté avec de l'abattement et des saignements excessifs après la castration. Le patient a développé de l'anémie hémolytique et le diagnostic a révélé l'infection par le virus de l'immunodéficience féline et Mycoplasma hæmofelis. Ce cas peut servir de rappel de l'importance du dépistage de la présence de maladies infectieuses et de l'éducation des propriétaires sur la prévention et la gestion des maladies infectieuses félines.(Traduit par Isabelle Vallières).

Toxoplasma gondii, Dirofilaria immitis, feline immunodeficiency virus (FIV), and feline leukemia virus (FeLV) infections in stray and pet cats (Felis catus) in northwest China: co-infections and risk factors.

This study was conducted to estimate the prevalence of Toxoplasma gondii, Dirofilaria immitis, feline immunodeficiency virus (FIV), and feline leukemia virus (FeLV) infections among stray and pet cats in Lanzhou, northwest China, and to identify the influence of age, gender, and regions on seropositivity. T. gondii antibodies were examined in cat sera by the modified agglutination test (MAT). The circulating antigens of D. immitis and FeLV and specific antibodies to FIV were examined using kits commercially available. The overall prevalence of T. gondii, FIV, FeLV, and D. immitis was 19.34, 9.12, 11.33, and 3.04 %, respectively. For the genetic characterization of T. gondii genotypes in cats, genomic DNA was extracted from the seropositive cats and the T. gondii B1 gene was amplified using a semi-nested PCR. DNA samples giving positive B1 amplification were then genotyped using multilocus PCR-RFLP. Two T. gondii genotypes (ToxoDB#9 and ToxoDB#1) were identified. Results of the multivariate logistic regression analysis showed that older cats are more likely to be seropositive than juveniles for T. gondii, FIV, FeLV, and D. immitis. This is the first report of T. gondii genotypes in cats in northwest China. Moreover, the present study is the first study of retrovirus and D. immitis seroprevalence in cats in China. The results revealed that T. gondii, FIV, and FeLV infections are common in stray and pet cats in northwest China.

Prevalence and risk factors of gammaherpesvirus infection in domestic cats in Central Europe.

BACKGROUND: Gammaherpesviruses (GHVs) are a large group of dsDNA viruses that can infect humans and several animal species. The two human GHVs, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are known for their oncogenic properties in individuals with immunodeficiency. Recently, the first feline GHV, Felis catus gammaherpesvirus 1 (FcaGHV1) was discovered and frequently found in domestic cats in Australia, Singapore and the USA. FcaGHV1 is more likely to be detected in cats co-infected with the feline immunodeficiency virus (FIV). FINDINGS: The prevalence of FcaGHV1 in pet cats from Germany and Austria was 16.2 % (95 % CI = 12.38-20.02). The odds for GHV infection were greater for FIV positive (OR = 4.5), male (OR = 13.32) and older (OR = 2.36) cats. Furthermore, FcaGHV1 viral loads were significantly higher in FIV-infected cats compared to matched controls. CONCLUSIONS: GHV infections are common in domestic cats in Central Europe. The worldwide distribution of FcaGHV1 can be assumed. A potential role as a co-factor in FIV-induced pathogeneses is supported.

Age-related cognitive impairments in domestic cats naturally infected with feline immunodeficiency virus.

BACKGROUND: Age-related dementia has been documented in domestic cats; however, its interaction with naturally occurring feline immunodeficiency virus (FIV) infection has been investigated minimally. METHODS: Visuospatial working memory (VSWM) and problem-solving (PS) ability were evaluated in FIV-infected (n = 37) and control cats (n = 39) using two cognitive tasks tested serially, which assessed the ability of cats to remember the location of a baited container after a set delay, then evaluated the capability of the cats to manipulate the container to obtain the food within a time limit. Cats were categorized using 7 years of age as a cut-off to determine age-related differences. The relationship between cognitive performance and FIV viral load was investigated using real-time PCR cycle threshold (Ct ) values. RESULTS: Age significantly affected VSWM and PS ability. Younger cats had better VSWM performance and PS ability compared to older cats with the same FIV status. There was no difference between younger FIV-positive and negative cats in either part of the task. While older FIV-positive cats had significantly worse VSWM than older FIV-negative cats, no differences were found in PS ability. Additionally, Ct values predicted VSWM but not PS ability. CONCLUSION: Age-related cognitive impairments and FIV infection appear synergetic, causing greater cognitive deficits in older FIV-infected cats.

Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection.

HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

Neurobehavioral performance in feline immunodeficiency virus infection: integrated analysis of viral burden, neuroinflammation, and neuronal injury in cortex.

Human immunodeficiency virus (HIV) infection causes motor and neurocognitive abnormalities affecting >50% of children and 20% of adults with HIV/AIDS (acquired immunodeficiency syndrome). The closely related lentivirus, feline immunodeficiency virus (FIV), also causes neurobehavioral deficits. Herein, we investigated the extent to which FIV infection affected specific motor and cognitive tasks in conjunction with viral burden and immune responses within the brain. Neonatal animals were infected with a neurovirulent FIV strain (FIV-Ch) and assessed in terms of systemic immune parameters, viral burden, neurobehavioral performance, and neuropathological features. FIV-infected animals displayed less weight gain and lower blood CD4(+) T-cell levels than mock-infected animals (p < 0.05). Gait analyses disclosed greater gait width with increased variation in FIV-infected animals (p < 0.05). Maze performance showed that FIV-infected animals were slower and made more navigational errors than mock-infected animals (p < 0.05). In the object memory test, the FIV-infected group exhibited fewer successful steps with more trajectory errors compared with the mock-infected group (p < 0.05). Performance on the gait, maze, and object memory tests was inversely correlated with F4/80 and CD3 epsilon expression (p < 0.05) and with viral burden in parietal cortex (p < 0.05). Amino acid analysis in cortex showed that D-serine levels were reduced in FIV-infected animals, which was accompanied by diminished kainate and AMPA receptor subunit expression (p < 0.05). The neurobehavioral findings in FIV-infected animals were associated with increased gliosis and reduced cortical neuronal counts (p < 0.05). The present studies indicated that specific motor and neurocognitive abilities were impaired in FIV infection and that these effects were closely coupled with viral burden, neuroinflammation, and neuronal loss.

Methamphetamine and lentivirus interactions: reciprocal enhancement of central nervous system disease.

Use of methamphetamine is increasingly a significant factor for the spread of human immunodeficiency virus type 1, for in certain populations, there is a convergence of methamphetamine abuse with human immunodeficiency virus type 1 infection. Methamphetamine and human immunodeficiency virus type 1 are both individually neuropathogenic, and the neuropathology caused by these two agents occurs in overlapping brain regions. However, the biological interaction of methamphetamine with lentiviruses remains unknown. Here, we investigate the effects of simultaneous exposure of these two agents on disease progression using the feline immunodeficiency virus model. The study models the bingeing methamphetamine user with sequential and repeated episodes of use, which were interrupted by periods of abstinence. Methamphetamine exposure significantly accelerated and enhanced the severity of the feline immunodeficiency virus model-induced central nervous system functional pathology, as measured in delays in brainstem auditory evoked potentials. Reciprocally, feline immunodeficiency virus enhanced the severity of the methamphetamine-induced effects on brain monoamine neurotransmitter and dopamine transporter levels. The results of this study indicate that a dual potentiation occurred. That is, methamphetamine enhanced feline immunodeficiency virus model-induced central nervous system disease and feline immunodeficiency virus model enhanced the toxic effects of methamphetamine, heralding a significant concern for those individuals that are exposed to both agents.

The incidence of aggressive behavior in cats naturally infected with Feline Immunodeficiency Virus (FIV) and its interaction with FIV disease progression.

A study was undertaken to determine the possible interaction between aggressive behavior and Feline immunodeficiency virus (FIV) disease progression based on semi­quantitative viral load levels and health status in naturally FIV­infected cats. FIV status was determined in ninety­six owned and stray cats, using nested polymerase chain reaction (PCR). Aggressive tendencies were assessed based on observation and the cats' demeanor as determined by the owners and shelter caretakers. Results showed that forty­seven cats (49%) were PCR­positive for FIV infection and all aggressive cats were FIV­positive (100%). FIV infection was significantly linked to extreme aggressive tendencies and the extremely aggressive FIV­infected cats were more likely to have an unhealthy status compared to the non­aggressive individuals (p = 0.022). There was also a significant difference (p = 0.012) in the mean Cycle threshold (Ct) values between the aggressive and non­aggressive FIV­infected cats and also between the unhealthy FIV­infected cats with extreme aggressive tendencies and the healthy FIV­infected individuals without aggression (p = 0.001). Accordingly, results indicated that parameters associated with FIV disease progression are directly linked to aggression. The possible impact of FIV on the behavioral pattern of naturally infected cats should not be underestimated. However, there is an urgent need to conduct more experiments to support the assumptions about the possible exacerbation of aggression tendencies in naturally FIV­infected cats following the direct effect of FIV through the course of the infection.

Effects of Regulatory T Cell Depletion on NK Cell Responses against Listeria monocytogenes in Feline Immunodeficiency Virus Infected Cats.

Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo studies investigating the interplay between these two cell populations are lacking. We previously described innate immune defects in FIV-infected cats characterized by cytokine deficits and impaired natural killer cell (NK) and NK T cell (NKT) functions. In this study, we investigated whether in vivo Treg depletion by treatment with an anti-feline CD25 monoclonal antibody would improve the innate immune response against subcutaneous challenge with Listeria monocytogenes (Lm). Treg depletion resulted in an increased overall number of cells in Lm-draining lymph nodes and increased proliferation of NK and NKT cells in FIV-infected cats. Treg depletion did not normalize expression of perforin or granzyme A by NK and NKT cells, nor did Treg depletion result in improved clearance of Lm. Thus, despite the quantitative improvements in the NK and NKT cell responses to Lm, there was no functional improvement in the early control of Lm. CD1a+ dendritic cell percentages in the lymph nodes of FIV-infected cats were lower than in specific-pathogen-free control cats and failed to upregulate CD80 even when Treg were depleted. Taken together, Treg depletion failed to improve the innate immune response of FIV-infected cats against Lm and this may be due to dendritic cell dysfunction.

Prevalence and risk factors for Felis catus gammaherpesvirus 1 detection in domestic cats in Italy.

Felis catus gammaherpesvirus 1 (FcaGHV1), a novel gammaherpesvirus of domestic cats identified in 2014, has been detected in different countries demonstrating a worldwide distribution. The aim of this study was to establish the prevalence of FcaGHV1 in Italy using a molecular epidemiological approach. FcaGHV1 DNA was detected with virus-specific real-time PCR in ≃1% of 2659 feline blood samples tested. Analysis of risk factors showed that being male and coinfection with feline immunodeficiency virus (FIV) increase the likelihood of FcaGHV1 detection. One-third of FcaGHV1-positive cats also tested positive for FIV provirus, whereas coinfections with feline panleukopenia virus were not demonstrated. Further studies are necessary to confirm the risk factors for FcaGHV1 detection and the pathobiology of the virus.

Multiple, Independent T Cell Lymphomas Arising in an Experimentally FIV-Infected Cat during the Terminal Stage of Infection.

Our laboratory has serially reported on the virologic and immunopathologic features of a cohort of experimental feline immunodeficiency virus (FIV)-infected cats for more than eight years. At 8.09 years post infection (PI), one of these animals entered the terminal stage of infection, characterized by undulating hyperthermia, progressive anorexia, weight loss, and pancytopenia; the animal was not responsive to therapeutic interventions, necessitating euthanasia six weeks later (8.20 years PI). Subsequent analyses indicated that neoplastic lymphocytes infiltrated multiple cervical lymph nodes and a band-like region of the mucosal lamina propria within a segment of the intestine. Immunohistochemistry and T cell clonality testing determined that the nodal and intestinal lesions were independently arising from CD3 T cell lymphomas. In-situ RNA hybridization studies indicated that diffuse neoplastic lymphocytes from the cervical lymph node contained abundant viral nucleic acid, while viral nucleic acid was not detectable in lymphocytes from the intestinal lymphoma lesion. The proviral long terminal repeat (LTR) was amplified and sequenced from multiple anatomic sites, and a common clone containing a single nucleotide polymorphism was determined to be defective in response to phorbol myristate acetate (PMA)-mediated promoter activation in a reporter gene assay. This assay revealed a previously unidentified PMA response element within the FIV U3 region 3' to the TATA box. The possible implications of these results on FIV-lymphoma pathogenesis are discussed.

Systolic blood pressure, routine kidney variables and renal ultrasonographic findings in cats naturally infected with feline immunodeficiency virus.

Objectives Hypertension is a common cause of proteinuria in HIV-infected people. In cats, feline immunodeficiency virus (FIV) infection appears to be associated with proteinuria. Therefore, the results from systolic blood pressure (SBP) measurements in naturally infected FIV-positive cats were reviewed to assess whether hypertension contributes to the observed proteinuria in these cats. Ultrasonographic findings in FIV-positive cats were reviewed to complete renal assessment and to extend the scant knowledge on renal ultrasonography in cats. Methods Data from client-owned, naturally infected FIV-positive cats were retrospectively reviewed. To obtain a control group, records were reviewed from age-matched, privately owned, FIV-negative cats. Results Data from 91 FIV-infected and 113 control cats were compared. FIV-infected cats showed a significantly lower SBP ( P <0.0001) and significantly fewer FIV-infected cats were hypertensive (⩾160 mmHg) compared with control cats ( P = 0.025). The prevalence of renal azotaemia did not significantly differ between groups, although FIV-infected cats had significantly lower urine specific gravity (USG) ( P = 0.0273) and a higher incidence of USG below 1.035 ( P = 0.043). Urinary protein:creatinine ratio (UPC) was significantly higher in FIV-infected cats ( P = 0.0005) and proteinuria (UPC >0.4) occurred more frequently in FIV-infected cats ( P <0.001). Renal ultrasonography showed abnormalities in 60/91 FIV-infected cats, with hyperechogenic cortices in 39/91 and enlarged kidneys in 31/91. Conclusions and relevance Hypertension can be excluded as a common cause of renal damage leading to proteinuria in FIV-infected cats. Proteinuria and poorly concentrated urine are common in naturally infected FIV-positive cats, in contrast to azotaemia. Clinicians should cautiously interpret ultrasonographic abnormalities as these occur in over half of FIV-infected cats.

Effect of chronic FIV infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection.

The purpose of this study was to investigate the effect of chronic feline immunodeficiency virus (FIV) infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection. Six cats chronically infected with FIV-Glasgow8 (Group X) and six FIV-free cats (Group Y) were infected with M. haemofelis on Day 0 by intravenous blood inoculation. From Day 0 until Day 86 post-infection (pi), blood samples were collected for M. haemofelis and FIV provirus quantitative real-time PCR and haematology. Three of the six cats in each of Groups X and Y were randomly selected to receive marbofloxacin treatment (2 mg/kg PO q24 h) from Day 16 to 43 pi, with the remaining cats being untreated controls with no antibiotic treatment. The M. haemofelis copy numbers and haematological data were compared between Groups X and Y, and between marbofloxacin-treated and control cats using a Mann-Whitney U-test. M. haemofelis infection was associated with development of macrocytic hypochromic anaemia. In some cats, marked variation in M. haemofelis copy number over time (>100,000-fold difference within 48 h in some cats) and/or cycling of copy number was seen. No correlation was found between FIV provirus copy number and M. haemofelis copy number or haematological variables. No significant effect of chronic FIV infection on M. haemofelis copy number kinetics or haematological changes due to M. haemofelis infection was found, other than MCHC (P=0.03). Marbofloxacin treatment was associated with a significant decrease in M. haemofelis copy number (P=0.002), although consistent clearance of infection was not demonstrated. This study reveals the presence of marked fluctuations in M. haemofelis copy number kinetics in vivo and a significant response to marbofloxacin antibiotic treatment.

Leishmaniosis due to Leishmania infantum in a FIV and FelV positive cat with a squamous cell carcinoma diagnosed with histological, serological and isoenzymatic methods.

Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox) constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative), visceral (spleen and lymph nodes) and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot). The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis.

South African report of first case of chromoblastomycosis caused by Cladosporium (syn Cladophialophora) carrionii infection in a cat with feline immunodeficiency virus and lymphosarcoma.

This report describes a 6-year-old neutered male feline immunodeficiency-positive cat with repeated abdominal and thoracic effusions. The cat was diagnosed with and treated for lymphosarcoma but remission was short-lived and, on re-evaluation, a fungal peritoneal exudate was noted. Cytology of the organisms is described and the culture elucidated Cladosporium carrionii, an important cause of chromoblastomycosis. Treatment with itraconazole was unsuccessful in this case.

Evaluation of in vivo and in vitro interactions of feline immunodeficiency virus and feline leukemia virus.

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.

Disease progression and viral genome variants in experimental feline leukemia virus-induced immunodeficiency syndrome.

A fatal immunodeficiency syndrome with clinical and pathologic features similar to human AIDS is inducible in cats by experimental inoculation with a specific strain of feline leukemia virus (FeLV) called FeLV-FAIDS. The course of the feline disease is characterized by an age-dependent prodromal period during which a non-disease-specific, common form of proviral DNA is detected in bone marrow. Preceding clinical onset of immunodeficiency is production of high levels of specific, pathogenic variant genomes, primarily as unintegrated viral DNA, in bone marrow. Acute immunodeficiency syndrome (survival period approximately 3 months) is associated with a short prodromal period and appearance of a characteristic variant genome (variant A) that persists at high copy number as integrated and full-length unintegrated viral DNA in bone marrow. Chronic immunodeficiency syndrome (survival greater than 1 year) is marked by a longer prodromal period, a more gradual onset of severe clinical immunosuppression, and a predominance of other variant genomes that often contain substantial internal deletions. In both forms of the disease, tissue-specific replication of certain variant viruses is noted in the bone marrow, intestine, and lymph nodes. Evidence from in vitro and in vivo virus transmission studies indicates that the appearance of FeLV-FAIDS variant viruses reflects differential replication of viral genomes pre-existing in the inoculum rather than rapid de novo evolution of new variants within each animal. These results demonstrate that retrovirus-induced immunodeficiency disease in cats can be associated with and prefigured by the amplified replication of specific viral variants in target tissues.

Effects of incidental infections and immune activation on disease progression in experimentally feline immunodeficiency virus-infected cats.

Specific pathogen-free cats were experimentally infected with feline immunodeficiency virus (FIV) and subsequently exposed to common infectious pathogens and immune stimuli over a 3-year period. Cats with preexisting FIV infection showed signs of disease after exposure to Haemobartonella felis, Toxoplasma gondii, feline herpesvirus-1, and feline calicivirus similar to signs in non-FIV-infected cats, although they were more severe. No adverse effects of immunization with inactivated rabies virus vaccine and a synthetic polyproline immunogen were observed in either FIV-infected or non-FIV-infected cats, whereas the application of a diphtheria-tetanus-pertussis vaccine caused transient fever and lymphadenopathy in both groups of animals. Primary immune responses to pathogens or immunogens were usually delayed or diminished in FIV-infected compared with non-FIV-infected cats. Repeated infections and immune activation had no significant effects on the levels of FIV-specific antibodies or on the proportion of peripheral blood mononuclear cells (PBMCs) containing FIV proviral DNA. However, FIV-infected cats that were not exposed to immune stimuli had lower CD4+ T-lymphocyte numbers and lower CD4+/CD8+ T lymphocyte ratios at the end of the 3-year study than FIV-infected cats exposed to cofactors. The latter also had normal levels of interleukin-3 receptor (IL-2R) and major histocompatibility class II (MHC-II) antigen expression on PBMCs, while FIV-infected cats not exposed to cofactors had up-regulated IL-2R and down-regulated MHC-II antigen expression. It was concluded that repeated immune stimulation did not have a deleterious effect on the course of FIV-induced immunodeficiency.

Methamphetamine and HIV-1: potential interactions and the use of the FIV/cat model.

The interaction of methamphetamine with human immunodeficiency virus (HIV), the aetiologic agent of Acquired Immune Deficiency Syndrome (AIDS), has not been thoroughly investigated. However, increasingly, a larger proportion of HIV infected individuals acquire the virus through methamphetamine use or are exposed to this drug during their disease course. In certain populations, there is a convergence of methamphetamine use and HIV-1 infection; yet our understanding of the potential effects that simultaneous exposure to these two agents have on disease progression is extremely limited. Studying the interactions between methamphetamine and lentivirus in people is difficult. To thoroughly understand methamphetamine's effects on lentivirus disease progression, an animal model that is both clinically relevant and easily manipulated is essential. In this report, we identified potential problems with methamphetamine abuse in individuals with a concurrent HIV-1 infection, described the Feline Immunodeficiency Virus (FIV)/cat model for HIV-1, and reported our early findings using this modelling system to study the interaction of methamphetamine and lentivirus infections.