The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies.

Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats in vivo and established a dosage that would sustain effective blood levels for 24 h. In an experimental FIPV infection of cats, GS-441524 treatment caused a rapid reversal of disease signs and return to normality with as little as two weeks of treatment in 10/10 cats and with no apparent toxicity.

Polymorphisms in ERAP1 and ERAP2 are shared by Caninae and segregate within and between random- and pure-breeds of dogs.

Specific polymorphisms in the endoplasmic reticulum amino peptidase genes ERAP1 and ERAP2, when present with certain MHC class receptor types, have been associated with increased risk for specific cancers, infectious diseases and autoimmune disorders in humans. This increased risk has been linked to distinct polymorphisms in both ERAPs and MHC class I receptors that affect the way cell-generated peptides are screened for antigenicity. The incidence of cancer, infectious disease and autoimmune disorders differ greatly among pure breeds of dogs as it does in humans and it is possible that this heightened susceptibility is also due to specific polymorphisms in ERAP1 and ERAP2. In order to determine if such polymorphisms exist, the ERAP1 and ERAP2 genes of 10 dogs of nine diverse breeds were sequenced and SNPs causing synonymous or non-synonymous amino acid changes, deletions or insertions were identified. Eight ERAP1 and 10 ERAP2 SNPs were used to create a Sequenom MassARRAY iPLEX based test panel which defined 24 ERAP1, 36 ERAP2 and 128 ERAP1/2 haplotypes. The prevalence of these haplotypes was then measured among dog, wolf, coyote, jackal and red fox populations. Some haplotypes were species specific, while others were shared across species, especially between dog, wolf, coyote and jackal. The prevalence of these haplotypes was then compared among various canid populations, and in particular between various populations of random- and pure-bred dogs. Human-directed positive selection has led to loss of ERAP diversity and segregation of certain haplotypes among various dog breeds. A phylogenetic tree generated from 45 of the most common ERAP1/2 haplotypes demonstrated three distinct clades, all of which were rooted with haplotypes either shared among species or specific to contemporary dogs, coyote and wolf.

Genetic characterization of healthy and sebaceous adenitis affected Standard Poodles from the United States and the United Kingdom.

The degree of heterogeneity associated with geographic origin and sebaceous adenitis (SA) status in Standard Poodles from the United States (US) and the United Kingdom (UK) was assessed. Healthy and SA-affected Standard Poodles from the US and the UK shared a major mitochondrial DNA (mtDNA) haplotype and a single Y chromosome haplotype. However, minor mtDNA haplotypes and frequencies were somewhat different between US and UK dogs and were significantly less associated with SA than major haplotypes across both populations. The US and UK populations exhibited recent divergence from a common gene pool, based on allele frequencies of 24 highly polymorphic short tandem repeats and principle coordinates and cluster analyses of genotype frequencies. However, there was no differentiation between SA affected and unaffected dogs. Over 90% of US and UK Poodles shared a common dog leukocyte antigen (DLA) class II haplotype, but showed some differentiation in minor haplotype frequency. No difference was observed in haplotype heterozygosity between SA affected and unaffected dogs from the same country and no disease association for SA was found within the DLA region by a high density single nucleotide polymorphism (SNP) scan. Zygosity mapping in the DLA region of Poodles indicated much lower site-specific diversity than in an outbred population of street dogs from Bali, Indonesia, reflecting the degree that breed associated historical bottlenecks have reduced diversity in a polymorphic region of the genome. This study shows possible pitfalls in more extensive genome-wide association studies, such as case and control numbers, population stratification, the involvement of multiple genes, and/or the possibility that SA susceptibility is fixed or nearly fixed within the breed, which can reduce power to detect genetic associations.

Expanded dog leukocyte antigen (DLA) single nucleotide polymorphism (SNP) genotyping reveals spurious class II associations.

The dog leukocyte antigen (DLA) system contains many of the functional genes of the immune system, thereby making it a candidate region for involvement in immune-mediated disorders. A number of studies have identified associations between specific DLA class II haplotypes and canine immune hemolytic anemia, thyroiditis, immune polyarthritis, type I diabetes mellitus, hypoadrenocorticism, systemic lupus erythematosus-related disease complex, necrotizing meningoencephalitis (NME) and anal furunculosis. These studies have relied on sequencing approximately 300 bases of exon 2 of each of the DLA class II genes: DLA-DRB1, DLA-DQA1 and DLA-DQB1. In the present study, an association (odds ratio=4.29) was identified by this method between Weimaraner dogs with hypertrophic osteodystrophy (HOD) and DLA-DRB1∗01501. To fine map the association with HOD, a genotyping assay of 126 coding single nucleotide polymorphisms (SNPs) from across the entire DLA, spanning a region of 2.5 Mb (3,320,000-5,830,000) on CFA12, was developed and tested on Weimaraners with HOD, as well as two additional breeds with diseases associated with DLA class II: Nova Scotia duck tolling retrievers with hypoadrenocorticism and Pug dogs with NME. No significant associations were found between Weimaraners with HOD or Nova Scotia duck tolling retrievers with hypoadrenocorticism and SNPs spanning the DLA region. In contrast, significant associations were found with NME in Pug dogs, although the associated region extended beyond the class II genes. By including a larger number of genes from a larger genomic region, a SNP genotyping assay was generated that provides coverage of the extended DLA region and may be useful in identifying and fine mapping DLA associations in dogs.

Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis.

Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.

An international parentage and identification panel for the domestic cat (Felis catus).

Seventeen commercial and research laboratories participated in two comparison tests under the auspices of the International Society for Animal Genetics to develop an internationally tested, microsatellite-based parentage and identification panel for the domestic cat (Felis catus). Genetic marker selection was based on the polymorphism information content and allele ranges from seven random-bred populations (n = 261) from the USA, Europe and Brazil and eight breeds (n = 200) from the USA. Nineteen microsatellite markers were included in the comparison test and genotyped across the samples. Based on robustness and efficiency, nine autosomal microsatellite markers were ultimately selected as a single multiplex 'core' panel for cat identification and parentage testing. Most markers contained dinucleotide repeats. In addition to the autosomal markers, the panel included two gender-specific markers, amelogenin and zinc-finger XY, which produced genotypes for both the X and Y chromosomes. This international cat parentage and identification panel has a power of exclusion comparable to panels used in other species, ranging from 90.08% to 99.79% across breeds and 99.47% to 99.87% in random-bred cat populations.

Dog leucocyte antigen class II diversity and relationships among indigenous dogs of the island nations of Indonesia (Bali), Australia and New Guinea.

The genetic polymorphism at the dog leucocyte antigen (DLA) class II loci DQA1, DQB1 and DRB1 was studied in a large genetically diverse population of feral and wild-type dogs from the large island nations of Indonesia (Bali), Australia and New Guinea (Bali street dog, dingo and New Guinea singing dog, respectively). Sequence-based typing (SBT) of the hypervariable region of DLA-DRB1, -DQA1 and -DQB1 alleles was used to determine genetic diversity. No new DQA1 alleles were recognized among the three dog populations, but five novel DLA-DRB1 and 2 novel DLA-DQB1 allele sequences were detected. Additional unknown alleles were postulated to exist in Bali street dogs, as indicated by the large percentage of individuals (15%-33%) that had indeterminate DRB1, DQA1 and DQB1 alleles by SBT. All three groups of dogs possessed alleles that were relatively uncommon in conventional purebreds. The New Guinea singing dog and dingo shared alleles that were not present in the Bali street dogs. These findings suggested that the dingo was more closely related to indigenous dogs from New Guinea. Feral dog populations, in particular large ones such as that of Bali, show genetic diversity that existed prior to phenotypic selection for breeds originating from their respective regions. This diversity needs to be identified and maintained in the face of progressive Westernization. These populations deserve further study as potential model populations for the evolution of major histocompatibility complex alleles, for the study of canine genetic diversity, for the development of dog breeds and for studies on the comigration of ancestral human and dog populations.

Uveodermatologic (VKH-like) syndrome in American Akita dogs is associated with an increased frequency of DQA1*00201.

The Akita breed of dog is affected by a number of distinct immune-mediated diseases, including thyroiditis, sebaceous adenitis, pemphigus foliaceus, uveitis, polyarthritis, myasthenia gravis, and uveodermatologic (UV) syndrome. UV syndrome is manifested by progressive uveitis and depigmenting dermatitis that closely resembles the human Vogt - Koyanagi - Harada syndrome. This study examined the allelic diversity of the three DLA class II loci (DRB1, DQA1, and DQB1) in the American Akita dog, and the relationship of specific DLA class II alleles to the UV. Low allelic variation was demonstrated within genes of DLA class II. American Akita dogs possessed six of the reported 16 DQA1 alleles, but only eight of 61 reported alleles in DRB1 and nine of 47 reported alleles in DQB1. Almost one-half of American Akita dogs were homozygous for a single allele at DQA1 and up to a quarter at DRB1 and DQB1. DLA-DQA1*00201 was associated with a significantly higher relative risk (RR = 15.3) or odds ratio (OR = 15.99) for UV syndrome than other DLA class II alleles. No significant association was noted with haplotypes of DRB1, DQB1, and DQA1 alleles; DRB1*03201-DQA1*00201 trended toward significance. This study confirmed loss of DLA genetic diversity in the American Akita dog in common with other pure breeds of dog and suggested a role for certain DLA class II gene alleles in the pathogenesis of UV.

Frequency and distribution of alleles of canine MHC-II DLA-DQB1, DLA-DQA1 and DLA-DRB1 in 25 representative American Kennel Club breeds.

The frequency and distribution of dog leucocyte antigens (DLA) class II -DQA1, -DQB1 and -DRB1 alleles were determined for 25 American Kennel Club (AKC) registered dog breeds, representing 360 dogs from each of the seven major performance categories. Six to twenty-eight (average n=11) dogs were studied per group, with the exception of the Akita dog (n=94). All dogs were unrelated with no common grandparents based on AKC pedigree records (F-value <0.125). DLA class II allelic diversity was broad across breeds; 31/61 published DLA-DRB1 alleles, 11/18 published DLA-DQA1 alleles and 31/47 published DLA-DQB1 alleles were found among the 25 breeds. However, allelic diversity was severely limited within a breed. Seventeen of the DLA-DRB1 alleles were each found in only a single breed, and only seven alleles were shared by seven or more breeds. DLA-DRB1*00101 and DLA-DRB1*01501 were shared by 16 and 19 breeds, respectively. DLA-DQA1*00101 and DLA-DQA1*00601 alleles were shared by many breeds. The Rough Collie (DLA-DQA1*00901), English Setter (DLA-DQA1*00101) and Scottish Terrier (DLA-DQA1*00101) were monoallelic for DLA-DQA1. Eleven DLA-DQB1 alleles were each found only in a single breed and only seven alleles were shared by six or more breeds. DLA-DQB1*00201 and DLA-DQB1*02301 were shared by 17 and 18 breeds, respectively. Forty per cent of dogs typed were homozygous at DLA-DRB1, 52% at DLA-DQA1 and 44% at DLA-DQB1. Nine new DLA class II alleles were identified; three for DRB1 and six for DQB1. Comparison of our study of North American purebred dogs to previous European DLA surveys showed a similar use of common alleles consistent with known founder effects. However, more alleles were detected in European breeds, compared to their North American descendents, indicating that additional DLA class II diversity was lost when European breeds were established in North America.

The Kintamani dog: genetic profile of an emerging breed from Bali, Indonesia.

The Kintamani dog is an evolving breed indigenous to the Kintamani region of Bali. Kintamani dogs cohabitate with feral Bali street dogs, although folklore has the breed originating 600 years ago from a Chinese Chow Chow. The physical and personality characteristics of the Kintamani dog make it a popular pet for the Balinese, and efforts are currently under way to have the dog accepted by the Federation Cynologique Internationale as a recognized breed. To study the genetic background of the Kintamani dog, 31 highly polymorphic short tandem repeat markers were analyzed in Kintamani dogs, Bali street dogs, Australian dingoes, and nine American Kennel Club (AKC) recognized breeds of Asian or European origin. The Kintamani dog was identical to the Bali street dog at all but three loci. The Bali street dog and Kintamani dog were most closely aligned with the Australian dingo and distantly related to AKC recognized breeds of Asian but not European origin. Therefore, the Kintamani dog has evolved from Balinese feral dogs with little loss of genetic diversity.

Common virus infections in cats, before and after being placed in shelters, with emphasis on feline enteric coronavirus.

The purpose of this study was to determine the origin and subsequent spread of feline calicivirus (FCV), feline herpesvirus (FHV), and feline enteric coronavirus (FECV) in cats relinquished to shelters. FCV was isolated from the oral fauces of 11% of healthy cats upon entry, and isolation rates were highest for kittens (33%). FHV shedding was very low (4%) at the time of entry and occurred mainly in juveniles. FECV shedding was also common among newly relinquished cats (33%), especially older kittens and juveniles (90%). The subsequent spread of all three viruses was rapid and efficient in the shelter environment. Fifteen percent of cats were shedding FCV, 52% FHV, and 60% FECV after 1 week. More detailed studies were done with FECV shedding, which could be accurately quantitated. The amounts of FECV shed by infected cats ranged from 10(2)to 10(16)particles/swab of feces. FECV shedding was several logs higher in young kittens with primary infection than adult cats with primary infections. The mean levels of FECV shedding among adults were the same for primary and chronic infections. Although shelters were not the primary source of these viruses for many relinquished cats, factors intrinsic to the shelter environment were critical in amplifying shedding and spread to susceptible individuals. Extrinsic factors were especially important for the spread of FHV and FECV. FHV shedding rates increased from 4% to 50% in 1 week's time. The speed and magnitude of the increase in FHV shedding suggested that there was reactivation of latent infections as well as acquisition of new infections. FECV shedding increased 10 to 1,000,000 fold in 1 week among cats that were already infected at entry, and more than one-half of initially negative cats were shedding FECV a week later. Feline calicivirus infection was the least likely to spread in the shelter. The infection rate only increased from 11 to 15% in 1 week.

Disease outcome and cytokine responses in cats immunized with an avirulent feline infectious peritonitis virus (FIPV)-UCD1 and challenge-exposed with virulent FIPV-UCD8.

Eight cats were immunized with an avirulent strain of feline infectious peritonitis virus (FIPV)-UCD1, then challenge-exposed to a highly virulent cat passaged strain (FIPV-UCD8). Th1 and Th2 cytokine profiles in the peripheral blood mononuclear cells (PBMCs) were measured throughout in the experiment. No clinical signs of FIP were evident in the experimental cats after immunization. After challenge, the immunized cats demonstrated one of four clinical outcomes: (1) classical effusive FIP; (2) accelerated FIP; (3) non-effusive FIP, or (4) resistance to challenge. Only minor cytokine changes were observed following immunization, however, several cytokine changes occurred following challenge-exposure. The most noteworthy changes were in tumor necrosis factor-alpha (TNF-alpha) and interferon gamma (IFN-gamma) levels. Our preliminary findings suggest that immunity against FIP is associated with TNF-alpha and IFN-gamma response imbalance, with high TNF-alpha/low IFN-gamma mRNA responses favouring disease and low TNF-alpha/high IFN-gamma mRNA responses being indicative of immunity.

An epizootic of highly virulent feline calicivirus disease in a hospital setting in New England.

This article reports an outbreak of 24 cases of an unusually virulent feline calicivirus (FCV) infection in a small animal hospital. The circumstances and disease signs were very similar to those recently described in an outbreak of FCV hemorrhagic disease in Northern California (Vet. Microbiol. 73 (2000) 281). The virus entered the facility through shelter cats showing upper respiratory signs. Affected cats manifested high fever, anorexia, labored respirations, oral ulceration, facial and limb edema, icterus, and pancreatitis. The infection spread rapidly among the patients by contaminated animal caretakers and hospital equipment. One case of fomite transmission from an employee to a housecat was documented. Prior vaccination, even with multiple doses of FCV-F9-based live calicivirus vaccine, was not protective. Affected cats often required extensive supportive care for 7-10 days, and the overall mortality from death and euthanasia was 32%. The strain of FCV responsible for this outbreak was genetically and serologically distinct from the FCV strain responsible for a similar epizootic and the FCV-F9 strain contained in most vaccines. Outbreaks of this type are being reported with increasing frequency, and are often associated with the practice of treating sick shelter cats in private practices. Similar to the present epizootic, outbreaks of FCV hemorrhagic disease have been self-limiting, but require prompt application of strict quarantine, isolation, personnel sanitation, and disinfection procedures.

Analysis of genetic variation in 28 dog breed populations with 100 microsatellite markers.

Dog breeds were created by man choosing for select phenotypic traits such as size, shape, coat color, conformation, and behavior. Rigorous phenotypic selection likely resulted in a loss of genetic information. The present study extends previous dog population observations by assessing the genotypic variation within and across 28 breeds representing the seven recognized breed groups of the American Kennel Club (AKC). One hundred autosomal microsatellite markers distributed across the canine genome were used to examine variation within breeds. Resulting breed-specific allele frequencies were then used in an attempt to elucidate phylogeny and genetic distances between breeds. While the set of autosomal microsatellites was useful in describing genetic variation within breeds, establishing the genetic relatedness between breeds was less conclusive. A more accurate determination of breed phylogeny will likely require the use of single-nucleotide polymorphisms (SNPs).

Alternatives to blood as a source of DNA for large-scale scanning studies of canine genome linkages.

Participation and compliance are critical to the success of any large-scale study of canine disease using DNA markers. Most canine genetic studies rely upon DNA extracted from peripheral blood samples. We assessed the utility of buccal swab epithelial cells and toe nails as a source of DNA for use in genomic screening studies. Using eight multiplexed canine microsatellite markers, amplified DNA obtained from peripheral blood, and from freshly extracted buccal epithelial cells, and buccal swab DNA extracted and stored at 20 degrees C for 27 months or extracted from toe nails were compared for three dogs. The accuracy of the genotyping at each locus was identical for each preparation. Buccal swab DNA samples were readily and uniformly amplified and could be stored for years without loss of integrity. Each buccal swab provided sufficient DNA for more than 200 individual PCR reactions. Toe nails provided ample DNA for thousands of PCR reactions and had the added advantage of ease of storage of the original tissues. These studies demonstrate the potential utility of DNA derived from buccal swabs or nails in large-scale genomic scanning and marker linkage studies.

Evidence for modulated immune response to Anaplasma phagocytophila sensu lato in cats with FIV-induced immunosuppression.

Human granulocytic ehrlichiosis (HGE) is an emerging infectious disease in which some patients experience unusual opportunistic infections. In this study, cats infected with the HGE agent, Anaplasma phagocytophila s.l., had clinical granulocytic ehrlichiosis (GE), anti-nuclear antibodies and increased IFN-gamma mRNA. In FIV-immunosuppressed cats with GE, there was upregulated IL-10 transcription but not IFN-gamma. Cats with FIV had poor response to vaccines, regardless of GE status. This preliminary report demonstrates that cats with FIV-infection make a good model of ehrlichiosis in an immunocompromised host, and that viral immunosuppression may not increase the severity of ehrlichiosis but may attenuate immune responses to the pathogen.

PCR multiplexed microsatellite panels to expedite canine genetic disease linkage analysis.

Modern dog breeds possess large numbers of genetic diseases for which there are currently few candidate genes or diagnostic tests. Linkage of a microsatellite marker to a disease phenotype is often the only available tool to aid in the development of screening tests for disease carriers. Detection of linkage to a specific disease phenotype requires screening of large numbers of markers across known affected and unaffected animals. To establish high throughput genome scanning this study placed 100 canine microsatellite markers, arranged by fragment size and fluorescent dye label, into 12 PCR multiplexed panels. The highest degree of multiplexing was 11 markers per panel while the lowest was five markers per panel; each panel was run in one gel lane on automated DNA sequencers. Selection of the markers was based upon chromosomal or linkage group locations, degree of polymorphism, PCR multiplex compatibility and ease of interpretation. The marker set has an average spacing of 22.25 centiMorgan (cM). Marker polymorphism was evaluated across 28 American Kennel Club (AKC) recognized breeds. The utility of buccal swab vs. blood samples was also validated in this study as all template DNA was derived from swabs obtained and submitted by participating dog breeders and owners. The PCR multiplexed microsatellite panels and sampling method described in this report will provide investigators with a cost effective and expedient means of pursuing linkage studies of specific canine genetic diseases.

'Candidatus Mycoplasma haemominutum', a low-virulence epierythrocytic parasite of cats.

The phylogenetic position and some taxonomically relevant characteristics of a small, low-virulence bacterial parasite of cats are described. A 16S rDNA analysis revealed that the organism was in the Mycoplasma clade and was most closely related to a parasite of pigs previously designated Eperythrozoon suis. As the organism has not been cultured in vitro and is maintained in serial passage in cats in vivo, Candidatus status is proposed for this novel taxon as 'Candidatus Mycoplasma haemominutum'.

Virulence differences between two field isolates of feline immunodeficiency virus (FIV-APetaluma and FIV-CPGammar) in young adult specific pathogen free cats.

The goal of this study was to identify a strain of feline immunodeficiency virus (FIV) that would be more virulent for adult cats than the prototype FIV-APetaluma and, thereby, enhance the FIV infection model for HIV-1 related research. Diehl et al. reported that one clade C strain of FIV, FIV-CPGammar, was more virulent than other known FIV isolates. Mortalities from 58 to 100% were reported for kittens 12 weeks of age and less following intravenous inoculation. A more variable and somewhat less virulent disease course was observed in neonatal to 8-10-week-old kittens infected orally, intravaginally or intrarectally with this same isolate (Obert and Hoover, 2000). However, no studies have been done with FIV-CPGammar in adult cats. Therefore, the virulence of FIV-CPGammar for young adult cats was compared to that of FIV-APetalulma, the original FIV isolate. One group of five cats were inoculated intraperitoneally with 470 TCID(50) of FIV-CPGammar in the form of pooled plasma from acutely infected cats, while a second group was infected with plasma containing the 750 TCID50 of FIV-APetaluma. The cats were observed for 20 weeks for gross signs of disease, hematologic abnormalities, time of antibody appearance, and plasma and peripheral blood mononuclear cell (PBMC) associated virus levels. Viral RNA and proviral DNA were measured by a real-time PCR, sensitive to 50 copies per milliliter. The only outward sign of disease was lymphadenopathy, which occurred at a similar time and intensity in both groups of cats. Cats infected with FIV-CPGammar were more likely to be neutropenic and lymphopenic during the first 10-12 weeks of infection than cats infected with FIV-APetaluma. Both groups of cats showed similar overall declines in absolute mean CD4 cell counts and identical concomitant increases in CD8 cells. CD4/CD8 cell ratios were also similar. Antibody, as measured by an ELISA against recombinant FIV-TM antigen, appeared in all cats by 4 weeks post-infection. The most significant differences were in plasma viral RNA and PBMC proviral DNA levels. Cats infected with FIV-CPGammar had up to 100 times higher mean levels of viral RNA during the first few weeks of infection than cats infected with FIV-APetaluma. This difference was also mirrored in levels of proviral DNA in PBMC, which were significantly higher in the FIV-CPGammar infected cats. Plasma viral RNA and PBMC proviral DNA levels were virtually identical in both groups of cats at 20 weeks post-infection. However, proviral DNA in tissues such as thymus and popliteal lymph nodes was 10-fold or so higher in FIV-CPGammar infected cats at 20 weeks and histopathologic lesions were more severe. Based on these various parameters, we concluded that FIV-CPGammar was more virulent than FIV-APetaluma in young adult cats during the 20-week study period. However, we were not able to recreate the severe and rapidly progressive disease previously reported for kittens, suggesting an age-related resistance similar to that observed previously for FIV-APetaluma (George et al., 1993).