Paranasal sinus masses of Rocky Mountain bighorn sheep (Ovis canadensis canadensis).

This article describes 10 cases of paranasal sinus masses in Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Among 21 bighorns that were examined from 11 herds in Colorado, 10 individuals (48%) from 4 herds (36%) had masses arising from the paranasal sinuses. Affected animals included 9 of 17 females (53%) and 1 of 4 males (25%), ranging in age from approximately 2 years to greater than 10 years. Defining gross features of these masses included unilateral or bilateral diffuse thickening of the respiratory lining of the maxillary and/or frontal sinuses, with abundant seromucinous exudate in the affected sinus cavities. Defining histologic features of these masses included chronic inflammation and proliferation of mesenchymal and epithelial cells of the mucosa and submucosa. Epithelial changes included hyperplasia of mucosal epithelium, hyperplasia of submucosal glands and ducts, and neoplasia (adenocarcinoma). Mesenchymal changes included submucosal myxedema, submucosal fibroplasia/fibrosis, bone destruction, and neoplasia (myxomatous fibroma). Specific immunohistochemistry and polymerase chain reaction for Jaagsiekte sheep retrovirus and enzootic nasal tumor virus were performed with negative results.

Quantitative analysis of herpesvirus sequences from normal tissue and fibropapillomas of marine turtles with real-time PCR.

Quantitative real-time PCR has been used to measure fibropapilloma-associated turtle herpesvirus (FPTHV) pol DNA loads in fibropapillomas, fibromas, and uninvolved tissues of green, loggerhead, and olive ridley turtles from Hawaii, Florida, Costa Rica, Australia, Mexico, and the West Indies. The viral DNA loads from tumors obtained from terminal animals were relatively homogeneous (range 2-20 copies/cell), whereas DNA copy numbers from biopsied tumors and skin of otherwise healthy turtles displayed a wide variation (range 0.001-170 copies/cell) and may reflect the stage of tumor development. FPTHV DNA loads in tumors were 2.5-4.5 logs higher than in uninvolved skin from the same animal regardless of geographic location, further implying a role for FPTHV in the etiology of fibropapillomatosis. Although FPTHV pol sequences amplified from tumors are highly related to each other, single signature amino acid substitutions distinguish the Australia/Hawaii, Mexico/Costa Rica, and Florida/Caribbean groups.

Intracellular targeting of walleye dermal sarcoma virus Orf A (rv-cyclin).

Walleye dermal sarcoma virus (WDSV) induces tumors and allows or possibly directs tumor regression. WDSV encodes a putative cyclin homologue, Orf A, and six variant Orf A transcripts have been identified. Northern analysis indicated that a 3.3-kb transcript, encoding full-length Orf A, is the predominant transcript in developing, but not regressing, tumors. Three Orf A proteins, one full-length and two amino-truncated forms, were expressed in mammalian and piscine cells, and their intracellular locations were determined. The full-length form was nuclear and concentrated in interchromatin granule clusters, defined by colocalization with SC-35. The amino-truncated forms were cytoplasmic. Fusion of amino-terminal portions of Orf A to a heterologous protein demonstrated that residues 1-112 were necessary for nuclear localization. Mutation of aa K80 and/or E110 disrupted nuclear localization, suggesting a mechanism similar to that of cellular A- and D-type cyclins for its nuclear import.

Three closely related herpesviruses are associated with fibropapillomatosis in marine turtles.

Green turtle fibropapillomatosis is a neoplastic disease of increasingly significant threat to the survivability of this species. Degenerate PCR primers that target highly conserved regions of genes encoding herpesvirus DNA polymerases were used to amplify a DNA sequence from fibropapillomas and fibromas from Hawaiian and Florida green turtles. All of the tumors tested (n = 23) were found to harbor viral DNA, whereas no viral DNA was detected in skin biopsies from tumor-negative turtles. The tissue distribution of the green turtle herpesvirus appears to be generally limited to tumors where viral DNA was found to accumulate at approximately two to five copies per cell and is occasionally detected, only by PCR, in some tissues normally associated with tumor development. In addition, herpesviral DNA was detected in fibropapillomas from two loggerhead and four olive ridley turtles. Nucleotide sequencing of a 483-bp fragment of the turtle herpesvirus DNA polymerase gene determined that the Florida green turtle and loggerhead turtle sequences are identical and differ from the Hawaiian green turtle sequence by five nucleotide changes, which results in two amino acid substitutions. The olive ridley sequence differs from the Florida and Hawaiian green turtle sequences by 15 and 16 nucleotide changes, respectively, resulting in four amino acid substitutions, three of which are unique to the olive ridley sequence. Our data suggest that these closely related turtle herpesviruses are intimately involved in the genesis of fibropapillomatosis.

Detection of a novel bovine lymphotropic herpesvirus.

Degenerate PCR primers which amplify a conserved region of the DNA polymerase genes of the herpesvirus family were used to provide sequence evidence for a new bovine herpesvirus in bovine B-lymphoma cells and peripheral blood mononuclear cells (PBMC). The sequence of the resultant amplicon was found to be distinct from those of known herpesvirus isolates. Alignment of amino acid sequences demonstrated 70% identity with ovine herpesvirus 2, 69% with alcelaphine herpesvirus 1, 65% with bovine herpesvirus 4, and 42% with bovine herpesvirus 1. Phylogenetic analysis placed this putative virus within the tumorigenic Gammaherpesvirinae subfamily, and it is tentatively identified as bovine lymphotropic herpesvirus. This novel agent was expressed in vitro from infected PBMC, and cell-free supernatants were used to transfer infection to a bovine B-cell line, BL3. Analysis, with specific PCR primers, of DNA from bovine PBMC and lymphoma cells identified infection in blood of 91% of adult animals (n = 101), 63% of lymphomas (n = 32), and 38% of juveniles (n = 13). Of the adults, herpesvirus infection was present in 94% of animals that were seropositive for bovine leukemia virus (BLV) (n = 63) and in 87% of BLV-seronegative animals (n = 38). Of the seropositive group, 17 animals exhibited persistent lymphocytosis, and 100% of these were herpesvirus positive by PCR. A role for bovine lymphotropic herpesvirus as a cofactor in BLV pathogenesis is considered.

Transcriptional analysis of walleye dermal sarcoma virus (WDSV).

Walleye dermal sarcoma virus (WDSV) is a complex retrovirus associated with dermal sarcomas of walleye that develop and regress on a seasonal basis. WDSV contains, in addition to gag, pol, and env, three open reading frames (ORFs) designated ORF A, ORF B, and ORF C. The polymerase chain reaction technique was used to amplify and clone cDNAs representing subgenomic viral mRNAs isolated from developing (fall) and regressing (spring) tumors. Nine different singly or multiply spliced viral transcripts were identified and all were found to utilize a common 5' leader sequence. This leader sequence is spliced to the pol/env junction or downstream of env to generate singly spliced transcripts. Multiply spliced transcripts contain the 5' leader, the pol/env junction, and sequences derived from the 3' end of the genome. One multiply spliced transcript was isolated with the potential to encode the full-length ORF A protein. In addition, WDSV produced mRNAs that utilize alternative splice acceptor sites which would allow synthesis of five variant forms of the ORF A protein. In contrast, the ORF B protein is postulated to arise from a singly spliced transcript with the potential to encode the entire open reading frame. Spliced subgenomic transcripts representing ORF C mRNAs were not identified, suggesting that ORF C may be encoded from the full-length viral genomic transcript. We estimate that at least a 100-fold lower amount of the accessory/regulatory subgenomic transcripts exists in developing vs regressing tumors. These results demonstrate that WDSV undergoes an elaborate pattern of mRNA splicing similar to that of other complex retroviruses.

Analysis of FeLV-FAIDS provirus burden and productive infection in lymphocyte subsets in vivo.

To help elucidate the immunopathogenesis of feline leukemia virus (FeLV)-induced immunodeficiency we studied the tropism of viruses derived from the FeLV-FAIDS isolate for lymphocyte subpopulations in cats. FeLV-FAIDS is composed of a replication-competent virus typical of subgroup A FeLV (prototype, clone 61E) and a family of replication-defective but immunopathogenic variant viruses (prototype, clone 61C). We sorted CD4+, CD8+, and IgG+ lymphocytes to > or = 97% purity and analyzed viral load in each cell population via genome-specific semiquantitative PCR. Both the 61E and 61C viruses were tropic for CD4+ and CD8+ T cells as well as IgG+ B lymphocytes in blood and lymph node. High provirus burden were established for both virus genomes-ranging from 0.3 to > 2 copies/cell. To identify the fraction of circulating cells which expressed viral antigen in vivo, we developed a flow cytometric method to simultaneously label blood leukocytes for surface immunophenotype and intracytoplasmic FeLV CA (p27 Gag). These experiments established that 20 to 60% of CD4+, CD8+, and IgG+ lymphocytes and > 85% of monocytes and granulocytes expressed FeLV p27 intracellularly. Thus the in vivo target cells for FeLV-FAIDS infection are manifold and include CD4+ and CD8+ T cells, B cells, and myeloid cells.

Replication kinetics and cell tropism of an immunosuppressive feline leukaemia virus.

To elucidate in vivo cell tropism and infection kinetics of an immunodeficiency-inducing isolate of feline leukaemia virus (FeLV-FAIDS), we quantified the two major genotypes comprising FeLV-FAIDS [the replication-competent common form (clone 61E) and the replication-defective variant (clone 61C)] in lymphocyte and leukocyte populations from infected cats. Micromagnetic separation of cell subsets, virus genome-specific PCR and flow cytometry were used to demonstrate the following sequence of events in infected animals: (i) very early replication of both 61E and 61C in CD4 T cells (provirus burden 0.2 to 1 copy/cell at 2-4 weeks post-infection); (ii) lower magnitude replication of both viruses in CD8 T cells and B cells during this initial phase of infection; (iii) plateauing of CD4 cell virus burden accompanied by escalation in CD8 and B cell provirus burdens after 4 weeks; (iv) extensive infection of haemopoietic and circulating myeloid cells. FeLV-FAIDS 61E and 61C replication kinetics and lymphocyte tropisms were similar in blood and lymph nodes, where provirus burdens ranged from 0.15 to 1.0 copy/cell. Moreover, virus infection was productive; 8-48 percent of blood lymphocytes, 35-81 percent of node lymphocytes and 53-98 percent of bone marrow cells expressed FeLV capsid antigen (p27 Gag). These findings suggest that the immunosuppressive potency of FeLV-FAIDS reflects the unique cytopathicity rather than unique cytotropism of its 61C (versus 61E) component.

Prospective characterization of the clinicopathologic and immunologic features of an immunodeficiency syndrome affecting juvenile llamas.

The clinicopathologic and immunologic features of 15 llamas affected with juvenile llama immunodeficiency syndrome (JLIDS) are described. Healthy adult (n = 10) and juvenile (n = 10) llamas served as controls. JLIDS llamas were characterized by wasting, and clinically apparent, repeated infections were frequently observed. The median age at which a health problem was first perceived was 11.6 months. All 15 affected llamas died or were killed, and JLIDS was confirmed at necropsy. The median duration of illness was 3.5 months. Lymphocyte blastogenesis assays showed suppressed responses (particularly to Staphylococcus sp. Protein A) in JLIDS llamas. No evidence of retroviral infection was detected. Mild, normocytic, normochromic, non-regenerative anemia, low serum albumin concentration and low to low-normal globulin concentrations were typically found on initial clinical evaluation. Lymph node biopsies showed areas of paracortical depletion. All llamas affected with JLIDS had low serum IgG concentrations, pre-vaccination titers against Clostridium perfringens C and D toxoids of < or = 1:100, and no titer increase following vaccination.

Immunodeficiency syndrome associated with wasting and opportunistic infection in juvenile llamas: 12 cases (1988-1990).

Immunodeficiency was diagnosed as the cause of severe debilitating disease characterized by weight loss, failure to grow, and persistent infections that failed to respond to treatment in 12 young llamas. The llamas were affected after maternal-acquired immunity had decreased; failure of passive transfer of immunoglobulins thus was not suspected. Areas of lymph nodes containing T lymphocytes were hypocellular, suggesting T-cell involvement. High serum immunoglobulin concentrations were not found, despite the existence of infectious disease, suggesting at least secondary B-cell involvement. Results of lymphocyte blastogenesis assays were suggestive of B- and T-cell involvement. It was not possible to determine whether the condition was inherited or acquired.

Structure and pathogenicity of individual variants within an immunodeficiency disease-inducing isolate of FeLV.

We previously described the molecular cloning of a replication-defective variant of feline leukemia virus (FeLV) that induced fatal immunodeficiency in cats. Eighteen proviruses have now been molecularly cloned from cats inoculated with the original isolate (FeLV-FAIDS) or its in vivo passages. Three were replication-competent and each of these was noncytopathic for the feline T-cell line, 3201. Replication of the prototype, FeLV-61E, in cats was associated with development of T cell tumors in some cats. The remaining 15 proviruses were replication-defective, but each of six of these tested was found to be cytopathic for 3201 cells when rescued with the noncytopathic helper virus, 61E. Three defective/helper virus mixtures were inoculated into cats and all induced fatal immunodeficiency, but with varied efficiency and kinetics. Each of these virus mixtures was attenuated relative to a mixture containing 61E and the intestine-targeted, FeLV-FAIDS-61C prototype defective molecular clone. Furthermore, one replication-competent virus chimera generated using the envelope and LTR of the defective pathogenic variant was incapable of inducing viremia in cats. The observed differences in the biological activity between the defective viruses could be attributed to no more than 10 scattered amino acid changes in envelope and either one or two nucleotide changes in the LTR.

Protection against feline leukemia virus infection by use of an inactivated virus vaccine.

The protective immunity induced by 3 experimental FeLV vaccines were evaluated: Prototype inactivated FeLV vaccine developed from a molecularly cloned FeLV isolate (FeLV-FAIDS-61E-A); a mixture of immunodominant synthetic peptides corresponding to regions of the FeLV-Gardner-Arnstein-B (FeLV-GA-B) envelope proteins; and an adjuvant-disrupted but non-activated virus prepared from a non-cloned FeLV field isolate comprised of subgroup A and B viruses (FeLV-05821-AB). Included as controls were parallel groups of cats inoculated with adjuvants alone or with an established commercial FeLV vaccine. After each inoculation and after virulent virus challenge exposure, sera from all cats were assayed for ELISA-reactive antibody against purified FeLV, FeLV neutralizing (VN) antibody, and FeLV antigenemia/viremia--viral p27 antigen in serum and within circulating leukocytes. Immunity was challenged by oral/nasal exposure of vaccinated and control cats with FeLV-FAIDS-61E-A or FeLV-05821-AB, an infective, noncloned, tissue-origin, FeLV field isolate containing subgroup-A and -B viruses. Vaccine-induced immunity was assessed by comparing the postchallenge-exposure incidence of persistent viremia and the pre- and postchallenge exposure titers of VN and ELISA antibody in cats of the control and vaccine groups. The percentage of cats, that resisted development of persistent viremia after FeLV challenge exposure and the preventable fraction (PF) for the vaccine groups (which adjusts for the severity of the challenge and the degree of innate resistance in the controls) were as follows: adjuvant controls, 26%; FeLV-FAIDS-61E-A inactivated virus vaccine, 95% (PF = 93.2%); FeLV-GA-B peptide vaccine, 5% (-28.4%); FeLV-05821-AB noninactivated vaccine, 67% (55.4%); and commercial FeLV vaccine, 35% (12.2%). The prechallenge exposure mean VN antibody titer for each group was: less than 1:8 in the adjuvant controls; 1:43 in the FeLV-FAIDS-61E-A-vaccinated cats; less than 1:8 in the peptide-vaccinated cats; 1:38 in the noninactivated virus-vaccinated cats group; and 1:12 in the cats vaccinated with the commercial vaccine. Thus, induction of VN antibody in the vaccinated cats, although modest, appeared to be correlated with induction of protective immunity as defined by resistance to FeLV challenge exposure. Results of these studies indicate that inoculation of cats with an experimental inactivated virus vaccine prepared from a molecularly cloned FeLV isolate was most effective in stimulating protective immunity against heterologous and homologous FeLV challenge exposure.

Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS.

Within the fatal immunodeficiency disease-inducing strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to acutely pathogenic, most of the latter of which are also replication defective (clone 61C is the prototype). Mixtures of 61E and 61C virus and chimeras generated between them, but not 61E alone, killed feline T cells. T-cell killing depended on changes within a 7-amino-acid region near the C terminus of the gp70 env gene or was achieved independently by changes within a 109-amino-acid region encompassing the N terminus of gp70. The carboxy-terminal change was also sufficient for induction of fatal immunodeficiency disease in cats. Other changes within the 61C gp70 gene enhanced T-cell killing, as did changes in the long terminal repeat, the latter of which also enhanced virus replication. T-cell killing correlated with high levels of intracellular unintegrated and proviral DNA, all of which were blocked by treatment of infected cells with sera from 61C-immune cats or with a neutralizing monoclonal antibody. These findings indicate that T-cell killing is a consequence of superinfection and that the mutations in env critical to pathogenicity of the immunosuppressive variant result in a failure to establish superinfection interference in infected cells.

Selective impairment of humoral immunity in feline leukemia virus-induced immunodeficiency.

We used a panel of in vitro assays to investigate the nature of immune dysfunction in cats infected with FeLV-FAIDS, a naturally occurring, molecularly cloned feline leukemia virus (FeLV) isolate which induces a fatal immunodeficiency syndrome in infected cats. During the asymptomatic period preceding immunodeficiency disease, we were unable to detect any deficits in concanavalin A-induced blastogenesis, xenogeneic mixed-lymphocyte reaction assays, stimulation of lymphocytes by soluble protein antigen, and cytotoxic T lymphocyte assays. However, during this period humoral immune responses in the FeLV-FAIDS-infected cats were dramatically impaired. As early as 9 weeks after virus inoculation, the ability to mount either an IgM or IgG response to soluble protein antigens was lost. Neither B cell function, as assessed by lipopolysaccharide-induced blastogenesis or circulating B cell numbers, as assessed by immunofluorescence, differed between infected and control cats. These results suggest that FeLV-FAIDS infection may impair a subpopulation of T helper cells, that provides help for the production of antibody. Consistent with earlier observations of cats naturally infected with FeLV, our results indicate that early impairment of humoral immunity is an important component of the immunodeficiency syndrome induced by FeLV in cats.

Flow cytometric analysis of T-lymphocyte subsets in cats.

We report a rapid, reliable method for the immunophenotype analysis of feline lymphocytes. Fluorescein isothiocyanate (FITC) conjugated to murine monoclonal antibodies f43, Fel 7 and fCD8 was used to identify phenotypes corresponding to feline T-cells, CD4+ T cells and CD8+ T cells. For isolation of white blood cells, whole blood lysis was faster, less variable and required much less sample than density gradient separation. To identify feline CD4+ and CD8+ cells simultaneously, directly conjugated FITC-fCD8 and phycoerythrin (PE) fCD4 (Fel 7) were used in two-color analysis. The two T cell sub-populations were non-overlapping. Dual-label and single-label values were not significantly different. Mean lymphocyte subset percentages in conventional and specific-pathogen-free (SPF) cats did not differ significantly. These values were: pan T lymphocytes (f43), 54.8%, CD4+ cells (Fel 7), 33.9%, and CD8+ cells (fCD8), 19.1%. Mean CD4/CD8 ratio was 1.9 in normal cats; the range was 1.2-2.6.

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.

Lymphocyte subset alterations and viral determinants of immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS.

The FeLV-FAIDS strain of feline leukemia virus consistently induces fatal immunodeficiency. To investigate the immunopathogenesis and viral genetic determinants responsible for the induction of immunodeficiency disease in vivo, we have generated chimeras between the two major viral genomes in the original virus isolate, designated common form clone 61E and major variant clone 61C, which were molecularly cloned directly from DNA of the same animal and tissue. Each of three 61E/C chimeras, containing at minimum a 34-amino-acid segment (including a 6-amino-acid insertion and one amino acid substitution) near the C terminus of the 61C surface glycoprotein (gp70), induced fatal immunodeficiency disease in all (12 of 12) infected animals over a course of 33 +/- 10 weeks. By contrast, animals infected with virus 61E, although persistently antigenemic, remained asymptomatic throughout a 48-week observation period. Beginning 14 weeks after infection, a significant decrease (8 to 10%) in the percent of circulating CD4+ T lymphocytes developed in the 61E/C chimera-infected cats, compared with either 61E-infected or control animals. At this time, no significant changes were seen in CD8 cells, B cells, or mitogen-induced blastogenesis. Prior to this initial decline in CD4 cells, the ability of all antigenemic 61E/C-infected cats to generate a primary antibody response to the T-cell-dependent antigen keyhole limpet hemocyanin was markedly impaired, whereas all 61E-infected cats, one 61E/C-infected but nonviremic cat, and all uninfected control cats produced normal antibody responses. The results reported here demonstrate that a major determinant of in vivo immunodeficiency induction by FeLV-FAIDS is contained within a 34-amino-acid C-terminal segment of its surface glycoprotein and that this gp70 alteration determines the early and persistent deficits in CD4+ T lymphocytes and T-cell-dependent antibody responses. We hypothesize that these early immunologic alterations could result from early deletion of a CD4+ helper T-cell subset.

Characterization and significance of delayed processing of the feline leukemia virus FeLV-FAIDS envelope glycoprotein.

FeLV-FAIDS, an immunodeficiency-inducing isolate of feline leukemia virus, is composed of a pathogenic but replication-defective genome (molecular clone 61C) and a replication-competent but non-immunodeficiency-inducing variant genome (molecular clone 61E). The chimeric virus EECC, composed of the 5' gag-pol of 61E fused to the env-3' LTR of 61C, also induces immunodeficiency. The 61C (or EECC) gp80 can be distinguished from that of 61E on the basis of antigenic recognition, size, and rate of posttranslational processing. We found that the nascent precursor polypeptides of the two viruses were the same size; however, the 61E gp80 rapidly shifted to a smaller size and was subsequently cleaved to gp70, whereas EECC gp80 maintained its nascent size and was cleaved to gp70 only after a prolonged time. Endo-beta-N-acetyl glucosaminidase H and N-glycanase digestions of newly formed glycoproteins resulted in a similar banding pattern for both viruses, indicating that both contained the same number of oligosaccharide side chains and that all of these were high mannose sugars. The metabolic inhibitors of glycosylation, castanospermine or N-methyldeoxynojirimycin, prevented both the rapid trimming of 61E gp80 and its cleavage to gp70. Treatment with mannosidase inhibitors, however, did not affect 61E gp80 processing or size, suggesting that retention of glucose residues on EECC was responsible for these distinguishing properties of the glycoprotein. The pathological consequence of aberrant viral glycoprotein processing was evaluated in feline 3201 T lymphocytes, which are infectable by both 61E and EECC but are killed only by EECC. As in fibroblasts, the EECC glycoprotein produced in lymphocytes was larger, antigenically distinct, and processed more slowly than was the glycoprotein of 61E. Castanospermine treatment of 61E-infected 3201 T cells, however, not only abrogated the antigenic differences between the 61E and EECC glycoproteins but also resulted in a cytopathic effect. Our results suggest that (i) intracellular accumulation of EECC envelope glycoprotein may occur consequent to retention of glucose residues on carbohydrate side chains and (ii) a strong correlation exists between delayed glycoprotein processing and cytopathicity in FeLV-FAIDS-infected T lymphocytes.