Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs.

Cisplatin is a platinum-containing cytotoxic drug indicated for the treatment of solid tumors in veterinary and human patients. Several of the algorithms used to standardize the doses of cytotoxic drugs utilize allometry, or the nonproportional relationships between anatomical and physiological variables, but the underlying basis for these relationships is poorly understood. The objective of this proof of concept study was to determine whether allometric equations explain the relationships between body weight, kidney weight, renal physiology, and clearance of a model, renally cleared anticancer agent in dogs. Postmortem body, kidney, and heart weights were collected from 364 dogs (127 juveniles and 237 adults, including 51 dogs ≥ 8 years of age). Renal physiological and cisplatin pharmacokinetic studies were conducted in ten intact male dogs including two juvenile and eight adult dogs (4-55 kg). Glomerular filtration rate (GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin clearance, and total cisplatin clearance were allometrically related to body weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar values of these diverse mass exponents suggest a common underlying basis for the allometry of kidney size, renal physiology, and renal drug handling.

Impaired glucose tolerance attenuates bone accrual by promoting the maturation of osteoblasts: Role of Beclin1-mediated autophagy.

Patients with type 2 diabetes mellitus (T2DM) experience a 1.5-3.5 fold increase in fracture risk, but the mechanisms responsible for these alterations in bone biomechanical properties remain elusive. Macroautophagy, often referred to as autophagy, is regulated by signaling downstream of the insulin receptor. Metabolic changes associated with the progression of glucose intolerance have been shown to alter autophagy in various tissues, but limited information is available in relation to bone cells. The aim of this study was to (a) investigate whether autophagy is altered in bone tissue during impaired glucose tolerance, and (b) determine how autophagy impacts osteoblast differentiation, activity, and maturation. Four-week-old, male C57BL/6 mice were fed a control (Con) or high fat (HF) diet for 2, 8, or 16 wks. Mice on the HF diet demonstrated elevated fasting blood glucose and impaired glucose tolerance. Reduced trabecular bone in the femoral neck was evident in the mice on the HF diet by 8 wks compared to Con mice. Histological evaluation of the tibia suggested that the high fat diet promoted terminal differentiation of the osteoblast to an osteocyte. This shift of the osteoblasts towards a non-mineralizing, osteocyte phenotype appears to be coordinated by Beclin1-mediated autophagy. Consistent with these changes in the osteoblast in vivo, the induction of autophagy was able to direct MC3T3-E1 cells towards a more mature osteoblast phenotype. Although these data are somewhat observational, further investigation is warranted to determine if Beclin1-mediated autophagy is essential for the terminal differentiation of the osteoblasts and whether autophagy is having a protective or deleterious effect on bone in T2DM.

Cardiac structure and function in female carriers of a canine model of Duchenne muscular dystrophy.

This investigation tested the hypothesis that carriers of golden retriever muscular dystrophy (GRMD), a genetically homologous condition of Duchenne muscular dystrophy (DMD), have quantifiable abnormalities in myocardial function, structure, or cardiac rhythm. Eleven GRMD carriers and four matched controls had cardiac evaluations and postmortem examinations. 24-h ECG Holter monitoring disclosed ventricular ectopy in 10 of 11 carriers and 2 of 4 controls. Conventional echocardiography failed to demonstrate significant differences between carriers and controls in systolic function. All carriers had multifocal, minimal to marked myofiber necrosis, fibrosis, mineralization, inflammation, and/or fatty change in their hearts. Immunohistochemistry revealed a mosaic dystrophin deficiency in scattered cardiac myofibers in all carriers. No controls had cardiac histologic lesions; all had uniform dystrophin staining. Despite cardiac mosaic dystrophin expression and degenerative cardiac lesions, GRMD carriers at up to 3 years of age could not be distinguished statistically from normal controls by echocardiography or 24-h Holter monitoring.

Transrectal ultrasound-integrated spectral optical tomography of hypoxic progression of a regressing tumor in a canine prostate.

The objective of this study was to evaluate if transrectal optical tomography implemented at three wavelength bands for spectral detection could monitor changes of the hemoglobin oxygen saturation (StO2) in addition to those of the total hemoglobin concentration ([HbT]) in lesions of a canine prostate, including an induced tumor modeling canine prostate cancer. Near-infrared (NIR) optical tomography was integrated with ultrasound (US) for transrectal imaging. Multi-spectral detection at 705_nm, 785_nm and 808_nm rendered measurements of [HbT] and StO2. Canine transmissible venereal tumor (TVT) cells were injected into the right lobe of a dog's prostate gland, which had a pre-existing cyst in the left lobe. Longitudinal assessments of the prostate were performed weekly over a 63-day duration by NIR imaging concurrent with grey-scale and Doppler US. Ultrasonography revealed a bi-lobular tumor-mass regressing from day-49 to day-63. At day-49 this tumor-mass developed a hypoxic core that became larger and more intense by day-56 and expanded further by day-63. The tumor-mass presented a strong hyper-[HbT] feature on day-56 that was inconsistent with US-visualized blood flow. Histology confirmed two necrotic TVT foci within this tumor-mass. The cyst appeared to have a large anoxic-like interior that was greater in size than its ultrasonographically delineated lesion, and a weak lesional elevation of [HbT]. On day-56, the cyst presented a strong hyper-[HbT] feature consistent with US-resolved blood flow. Histology revealed acute and chronic hemorrhage in the periphery of the cyst. The NIR imaging features of two other TVT nodules and a metastatic lymph node were evaluated retrospectively. Transrectal US-integrated spectral optical tomography seems to enable longitudinal monitoring of intra-lesional oxygenation dynamics in addition to the hemoglobin content of lesions in the canine prostate.

Gastritis in Alaskan racing sled dogs.

Alaskan racing sled dogs are a well-established model of exercise-induced gastric disease. The aim of this study was to define the temporal development of microscopical gastric lesions during long distance racing. Two groups of dogs were examined: group I comprised conditioned dogs that were exercising and group II were conditioned dogs not exercising. The gastric mucosa was examined endoscopically and sampled for routine histopathology and microscopical scoring, immunohistochemistry (IHC) and detection of apoptotic epithelial cells. Overall, group I dogs exhibited more significant epithelial lesions, including ulcers, compared with dogs in group II. Group II dogs exhibited the most severe mucosal inflammatory infiltrates. Although the intensity of inflammation differed, the nature of the inflammation was similar between groups, consisting of diffuse lymphocytic infiltration and a unique interface-type infiltrate that obscured the basement membrane zone and was accompanied by intraepithelial infiltration of lymphocytes. IHC confirmed the presence of CD3(+) T and CD79(+) B lymphocytes within the mucosal infiltrates; however, most of the intraepithelial and interface infiltrates were CD3(+) T cells. Spiral-shaped bacterial organisms were seen in the gastric tissues; however, their presence did not correlate with either the severity of epithelial lesions, inflammation or the pattern of interface inflammation. The number of apoptotic epithelial cells was widely variable and not significantly different between groups. These findings confirm previous observations that gastric ulcers develop in conditioned dogs under racing stress. The unique nature of the interface-type gastric inflammation is similar to that of human lymphocytic gastritis and may suggest an immune-mediated mechanism for the changes seen in Alaskan racing sled dogs.

Trans-rectal ultrasound-coupled spectral optical tomography of total hemoglobin concentration enhances assessment of the laterality and progression of a transmissible venereal tumor in canine prostate.

OBJECTIVES: To evaluate whether trans-rectal spectral optical tomography of total hemoglobin concentration (HbT) can image longitudinal and lateral developments of a canine transmissible venereal tumor (TVT) in a canine prostate. METHODS: A near-infrared (NIR) applicator was integrated with a trans-rectal ultrasound (TRUS) transducer to perform ultrasound (US)-coupled optical tomography of the canine prostate. Spectral detection at 785 and 830 nm enabled quantitation of HbT. Canine TVT cells were injected into the right lobe of a dog's prostate gland. Longitudinal imaging assessment of the post-injection prostate was performed by coupled US/NIR imaging over a 45-day duration. RESULTS: By day 7, NIR indicated TVT infiltration in the noninjected left prostatic lobe with the gray-scale US indistinct. By day 31, both NIR and gray-scale US revealed more widespread TVT involvement in the left than in the right lobe, as well as an extensive TVT mass in the caudal aspect of the gland, of which the peak HbT increased 3-fold and the mass volume grew exponentially over the 45-day duration. Increased blood supply to the mass was also observed on Doppler US. CONCLUSIONS: TRUS-coupled spectral optical tomography enhances assessment of the laterality and progression of prostate tumor compared with using gray-scale and Doppler TRUS.

Mannheimia haemolytica: bacterial-host interactions in bovine pneumonia.

Mannheimia haemolytica serotype S1 is considered the predominant cause of bovine pneumonic pasteurellosis, or shipping fever. Various virulence factors allow M haemolytica to colonize the lungs and establish infection. These virulence factors include leukotoxin (LKT), lipopolysaccharide, adhesins, capsule, outer membrane proteins, and various proteases. The effects of LKT are species specific for ruminants, which stem from its unique interaction with the bovine ß2 integrin receptor present on leukocytes. At low concentration, LKT can activate bovine leukocytes to undergo respiratory burst and degranulation and stimulate cytokine release from macrophages and histamine release from mast cells. At higher concentration, LKT induces formation of transmembrane pores and subsequent oncotic cell necrosis. The interaction of LKT with leukocytes is followed by activation of these leukocytes to undergo oxidative burst and release proinflammatory cytokines such as interleukins 1, 6, and 8 and tumor necrosis factor α. Tumor necrosis factor α and other proinflammatory cytokines contribute to the accumulation of leukocytes in the lung. Formation of transmembrane pores and subsequent cytolysis of activated leukocytes possibly cause leakage of products of respiratory burst and other inflammatory mediators into the surrounding pulmonary parenchyma and so give rise to fibrinous and necrotizing lobar pneumonia. The effects of LKT are enhanced by lipopolysaccharide, which is associated with the release of proinflammatory cytokines from the leukocytes, activation of complement and coagulation cascade, and cell cytolysis. Similarly, adhesins, capsule, outer membrane proteins, and proteases assist in pulmonary colonization, evasion of immune response, and establishment of the infection. This review focuses on the roles of these virulence factors in the pathogenesis of shipping fever.

Type I IFN response to Papiine herpesvirus 2 (Herpesvirus papio 2; HVP2) determines neuropathogenicity in mice.

Isolates of baboon alpha-herpesvirus Papiine herpesvirus 2 (HVP2) exhibit one of two distinct phenotypes in mice: extremely neurovirulent or apathogenic. Previous studies implicated the type I interferon (IFN) response as being a major factor in controlling infection by apathogenic isolates. To further investigate the possibility that the host IFN-beta response underlies the pathogenicity of the two HVP2 subtypes, the susceptibility of mice lacking the IFN-beta receptor (IFNAR(-/-)) to infection was examined. Apathogenic isolates of HVP2 (HVP2ap) replicated in IFNAR(-/-) primary mouse dermal fibroblast (PMDF) cultures as well as neurovirulent (HVP2nv) isolates. IFNAR(-/-) mice were also susceptible to lethal infection by HVP2ap isolates. Unlike Balb/c or parental 129 mice, LD(50) and ID(50) values for HVP2ap were the same in IFNAR(-/-) mice indicating that in these mice infection always progressed to death. HVP2ap replicated in the skin at the site of inoculation and invaded dorsal root ganglia as efficiently as HVP2nv in IFNAR(-/-) mice. Since the virion host shutoff (vhs) protein encoded by the UL41 gene of herpes simplex virus has been implicated in circumventing the host IFN-beta response and the phenotype of UL41 deletion mutants of HSV is very similar to that of HVP2ap isolates, the UL41 gene was deleted from HVP2nv (Delta 41) and replaced with the UL41 ORF from HVP2ap (Delta 41C). Like the parental HVP2nv virus, the Delta 41C recombinant replicated efficiently in Balb/c PMDFs and did not induce a strong IFN-beta response. The neuropathogenicity of the Delta 41C recombinant was also the same as the parental HVP2nv virus in Balb/c mice, indicating that the vhs protein does not underlie the different neuropathogenic phenotype of HVP2ap and HVP2nv. In contrast, the Delta 41 deletion virus induced a strong IFN-beta response but was still able to undergo multiple rounds of replication in PMDF cultures, albeit at a slower pace than the parental HVP2nv. This was reflected in vivo as the Delta 41 mutant had an LD(50) equivalent to that of the parental HVP2nv virus although the time to death was longer. These results indicate that while the vhs protein is involved in preventing and/or suppressing an IFN-beta response, it is not responsible for the ability of HVP2nv to overcome IFN-beta induced resistance of uninfected cells and does not underlie the divergent pathogenicity of the two HVP2 subtypes in mice.

Granulomatous and eosinophilic rhinitis in a cow caused by Pseudallescheria boydii species complex (Anamorph Scedosporium apiospermum).

A 2-year-old Hereford cow was presented to the teaching hospital for increased respiratory noise and bilateral bloody nasal discharge. A nodular rhinitis was detected clinically, and the nasal biopsy revealed a granulomatous and eosinophilic rhinitis with intralesional fungi. The cow was euthanized due to financial constraints. Grossly multifocal-to-coalescing, raised, ulcerated firm nodules were present in both nares. Histologically, the lamina propria was expanded by intense infiltrates of eosinophils, epithelioid macrophages, multinucleate giant cells, lymphocytes, and plasma cells. Associated with the inflammatory cells were variably sized, septate hyphae, 5-8 microm in diameter, admixed with numerous, terminal conidia, 6-30 microm in diameter, with a discrete outer wall identified by culture as Pseudallescheria boydii species complex (anamorph Scedosporium apiospermum). The infection was localized to the nasal cavity with no gross or microscopic evidence of a systemic dissemination.

Temporal progression of viral replication and gross and histological lesions in Balb/c mice inoculated epidermally with Saimiriine herpesvirus 1 (SaHV-1).

Saimiriine herpesvirus 1 (SaHV-1), an alphaherpesvirus enzootic in squirrel monkeys, is genetically related to monkey B virus and human herpes simplex virus (HSV). To study the temporal progression of viral spread and associated lesions, Balb/c mice were inoculated epidermally by scarification with a green fluorescent protein (GFP)-expressing recombinant strain of SaHV-1 and killed sequentially. Pinpoint ulcerative lesions in the inoculated epidermis progressed over a few days to unilateral or bilateral hindlimb paresis or paralysis, urinary and faecal incontinence, abdominal distension, hunched posture and eventual depression warranting euthanasia. Viral replication was present within epidermal keratinocytes, neurons of the dorsal root ganglia and thoracolumbar spinal cord, regional autonomic ganglia, lower urinary tract epithelium and colonic myenteric plexuses, as indicated by histological lesions and GFP expression. Almost all mice inoculated with 10(5) or 10(6) plaque-forming units (PFU) of SaHV-1 developed rapidly progressive disease. Two of eight mice given 10(4)PFU developed disease, but no mice receiving less than 10(4)PFU gave evidence of infection. Mice that showed no clinical signs also failed to develop an antiviral IgG response, indicating absence of active viral infection. For SaHV-1 inoculated epidermally, the ID(50), CNSD(50) and LD(50) values were identical (10(4.38)), indicating that successful infection by this route invariably resulted in lethal CNS (central nervous system) disease. Consistently severe disease in all infected animals, with regionally extensive distribution of viral replication, constituted a marked difference from the disease produced by intramuscular inoculation.

Clinicopathological characterization of monkey B virus (Cercopithecine herpesvirus 1) infection in mice.

The purpose of this study was to establish a small animal model for monkey B virus (BV) infection. Mice were inoculated intramuscularly with several BV isolates. Comparisons were based upon the doses required to produce infection (ID50), non-central nervous system (CNS) clinical disease (CS50), CNS disease (CNSD50) and lethal effect (LD50). Strains differed in respect of the dose required to produce clinical disease in BALB/c mice. C57BL/6 mice were more resistant than BALB/c mice to CNS disease. Skin lesions at the inoculation site consisted of epidermal necrosis, ulceration, serocellular crusts and underlying dermatitis. CNS lesions included marked inflammation in the ipsilateral dorsal root ganglion and lumbar spinal cord (point of viral entry). The distribution of the lumbar spinal cord lesions suggested viral entry via sensory afferent neurons, ventral motor tracts, or both. The lesions in the more cranial spinal cord segments suggested ascension to the brain via bilateral spinothalamic and spinoreticular tracts. Brain lesions included encephalitis with neuronal necrosis and white matter destruction located consistently at the base of the brainstem, the reticular system, and rostrally to the thalamus and hypothalamus. Viral antigen was detected immunohistochemically in the lesions. The results indicated an ascending encephalomyelitis syndrome similar to that produced by BV in man.

Diagnosis of infectious canine hepatitis virus (CAV-1) infection in puppies with encephalopathy.

Nine weaned Labrador Retriever puppies from a litter of 11 were presented with signs of acute central nervous system (CNS) disease that included ataxia and blindness. All puppies died. Gross examination of tissues from 2 puppies revealed regionally diffuse hemorrhages in the brain stem and swollen hemorrhagic lymph nodes. Light microscopic examination of hematoxylin and eosin-stained tissues showed numerous large, basophilic intranuclear inclusion bodies within CNS vascular endothelium and occasionally in individual hepatocytes. Immunohistochemical staining of the tissue was positive using an antibody against canine adenovirus-1. Virus isolation for infectious canine hepatitis virus was achieved using inoculated cell cultures. Polymerase chain reaction amplification of DNA from cell culture material revealed shared homology with other mammalian adenoviruses.

Juvenile nephropathy in two related Pembroke Welsh corgi puppies.

Juvenile nephropathy has been documented in many breeds. Two related Pembroke Welsh corgi puppies presented at three and five months of age, respectively, for evaluation of lethargy, diarrhoea, poor body condition, polyuria and proteinuria. Based upon the clinical presentation, urinalysis and serum biochemistry, chronic renal failure was diagnosed. Renal histopathology was consistent with juvenile nephropathy, revealing lesions similar to the juvenile renal disease of dobermann dogs. To the authors' knowledge, this is the first report of juvenile nephropathy in related Pembroke Welsh corgi dogs. Familial nephropathy should now be considered as a differential diagnosis in cases of young Pembroke Welsh corgi dogs presenting with clinical signs indicating renal failure.

Construction and in vivo detection of an enhanced green fluorescent protein-expressing strain of Saimiriine herpesvirus 1 (SaHV-1).

Saimiriine herpesvirus 1 (SaHV-1) is an alpha-herpesvirus of squirrel monkeys used in mice to study neural pathogenesis of herpesviruses. To trace dissemination of virus from a peripheral site of inoculation to the central nervous system tissues, a recombinant strain of SaHV-1 expressing enhanced green fluorescent protein (GFP) was constructed by site-specific insertion of a GFP expression cassette into a transcriptionally null point in the SaHV-1 genome. PCR and Southern blot confirmed insertion of a single GFP expression cassette into the target site of the SaHV-1 genome. The recombinant virus was shown to produce strong fluorescence in the cytoplasm of infected cells in vitro. Growth kinetic experiments demonstrated no differences between recombinant and wild type SaHV-1 in producing infectious progeny virions. The recombinant virus was comparable to wild type SaHV-1 in development of clinical disease, microscopic lesions and induction of an antibody response in mice following intramuscular inoculation. Using confocal microscopy, GFP expression was easily observed in formalin fixed, paraffin-embedded tissues of mice infected with the recombinant SaHV-1. This simple specimen processing technique preserves tissue morphology and allows detection of viral replication within various tissues of experimentally infected animals.

Comparative pathology of infections with baboon and African green monkey alpha-herpesviruses in mice.

The comparative pathology of Herpesvirus papio 2 (HVP2) of baboons and SA8 virus of African green monkeys relative to that of herpes simplex virus (HSV1) of man was investigated in young adult mice inoculated intramuscularly and observed for 21 days. The 50% infectious dose (ID(50)) for HVP2 was approximately 10(2.0) plaque-forming units (PFU), while the ID(50) for HSV1 and SA8 was 10(2.5) and 10(3.8), respectively. There were marked differences in the ability of these three viruses to invade the central nervous system (CNS) and cause clinical neurological disease. HSV1 produced neurological signs in a few animals given 10(6)PFU, but SA8 did not. In contrast, HVP2 readily invaded the CNS and produced fatal disease with doses as low as 10(2)PFU. Two isolates of HVP2 tested had a 50% CNS disease dose (CNSD(50)) of 10(2.5) and 10(3.0)PFU and an LD(50) of 10(3.8) and 10(4.3)PFU, respectively. Histopathological examination of tissue from HVP2-infected mice revealed severe lesions of inflammation and necrosis in the central, peripheral and autonomic nervous systems, as well as of other tissues including skin, adrenal glands and the gastrointestinal tract. Viral antigens were detected immunohistochemically in lesions. This study showed that while both HVP2 and SA8 could infect mice, there were marked differences in the ability of these two closely related viruses to cause clinical disease and CNS lesions. This murine model may prove useful in the investigation of viral or host determinants responsible for the varying neurovirulence of these simian alpha-herpesviruses.

Trigeminal and polyradiculoneuritis in a dog presenting with masticatory muscle atrophy and Horner's syndrome.

A 9-year-old, spayed female, Airedale Terrier was euthanatized and necropsied after a progressive clinical course that included Horner's syndrome of the left eye and unilateral atrophy of the masticatory muscles. Although gross lesions were limited, a polyradiculoneuritis and ganglionitis that was most severe in the trigeminal nerves and ganglia were confirmed histologically. The inflammatory infiltrate consisted predominantly of macrophages and B and T lymphocytes that were phenotypically confirmed by immunostaining. Horner's syndrome was the result of damage to postganglionic sympathetic fibers that were incorporated in segments of the inflamed trigeminal nerve and its ophthalmic branch. Histologically, the character and distribution of the inflammation was similar to previously described syndromes of suspected immune-mediated etiology in humans and animals.

Characterization of gross and histological lesions in Balb/c mice experimentally infected with herpesvirus saimiri 1 (HVS1).

Accidental B virus (Herpesvirus simiae) infection of human beings working with macaques is frequently fatal. However, the pathogenic potential of other similar simian alphaherpesviruses, such as the squirrel monkey virus Herpesvirus saimiri (HVS1), is virtually unknown. As part of an effort to develop a murine model for infections with these agents, Balb/c mice were inoculated intramuscularly in the left hindlimb with 10 to 10(6) plaque forming units (PFU) of HVS1. After observation for clinical signs of infection for 21 days, mice were killed and specimens collected for serology and histopathology. Mice receiving 510(3) PFU of HVS1 exhibited severe, pruritic, ulcerative skin lesions near the site of inoculation and developed unilateral or bilateral hindlimb paralysis with severe muscle atrophy. Histological lesions were characterized by a necrotizing dermatitis and folliculitis. Spinal cord lesions consisted of a non-suppurative myelitis affecting primarily the ipsilateral dorsal horn of the thoracolumbar spinal cord with occasional extension to ventral and contralateral spinal cord regions. Immunohistochemical labelling confirmed the presence of viral antigen within the lesions, and anti-HVS1 IgG concentrations were related to the occurrence of disease. HVS1 infection in some mice extended from the ipsilateral dorsal horn and funiculus into the ventral and contralateral grey and white matter, resulting in bilateral hindlimb paralysis. Thoracolumbar spinal cord lesions resolved without continued spread of the virus to cranial nervous system structures, i.e., cervical spinal cord and brain.

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.

T cells overexpressing interferon-gamma and interleukin-10 are found in both the thymus and secondary lymphoid tissues of feline immunodeficiency virus-infected cats.

Similar to human immunodeficiency virus type 1, feline immunodeficiency virus (FIV) replicates in the thymus of infected animals, causing marked alteration in thymic lymphocyte subpopulations. The immune phenotype and cytokine patterns in the thymus and secondary lymphoid tissues of FIV-infected cats were investigated. FIV infection caused an acute-stage transient reduction in CD4CD8 double-positive thymocytes, a marked increase in CD8 single-positive thymocytes, and formation of thymic B cell lymphoid follicles. Interferon (IFN)-gamma and interleukin (IL)-10 mRNA were up-regulated in both the thymus and lymph nodes of FIV-infected cats. Analysis of purified CD4 and CD8 cells revealed that CD4 cells produced most of the IL-10, whereas IFN-gamma was produced by both subsets. Quantitative-competitive reverse-transcription polymerase chain reaction analysis revealed that thymocytes, especially CD4CD8 thymocytes, had much greater levels of gag mRNA than did lymph node T cells. Thus, overexpression of IFN-gamma and IL-10 is a feature of the thymus and secondary lymphoid tissues of FIV-infected cats.