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Risk factors associated with the incidence of seroconversion to caprine arthritis-encephalitis virus in goats on California dairies.

Incidence of seroconversion to caprine arthritis-encephalitis virus (CAEV) was determined for 1,194 goats on 11 dairies, using 2 repeated annual herd tests for CAEV. Current life table methods were used to compare age-specific incidence of seroconversion for pasteurized milk-raised and unpasteurized milk-raised goats. Logistic regression models were used to determine the risk factors associated with CAEV seroconversion, and to estimate odds ratios for seroconversion for various factor levels. Goats raised by unpasteurized milk-feeding methods were 2.5 to 6.7 times more likely to seroconvert than were goats raised by pasteurized milk-feeding methods, depending on the method of comparison. Similarly, 61.6 to 85.0% of seroconversions in yearling goats possibly were attributable to unpasteurized milk feeding. Among yearling goats, CAEV seroconversion was associated with feeding method, breed, and source of goat (herd of origin) when the effect of dairy was considered. In addition to the 6.7 times greater risk of seroconversion for unpasteurized milk-raised goats, yearling goats of the Saanen and Toggenburg breeds were 2.2 and 3.3 times, respectively, more likely to seroconvert than were Alpine yearling goats. Yearling goats purchased from another source were less likely to seroconvert than were yearlings raised on the dairy where they were studied. Among goats > 1 year old, age was associated with risk of seroconversion. Goats that were 3 years old or were > or = 4 years old were 1.7 and 3.2 times, respectively, more likely to seroconvert than were 2-year-old goats, when adjusted for effect of dairy. The effects of dairy were significant (P < or = 0.001) in yearling and older goats.

Age Factors↗

Pestivirus is a common contaminant in maedi-visna and caprine arthritis-encephalitis virus stocks.

Eight different laboratory stocks of maedi-visna or caprine arthritis-encephalitis virus were examined for the presence of pestiviruses by a fixed-cell immunoperoxidase assay with polyclonal and monoclonal antibodies. All of the viral stocks examined were found to contain noncytopathic pestivirus contaminants. The panel of monoclonal antibodies could not type the isolates as being more related to bovine virus diarrhea virus or border disease virus. However, the results did indicate that all isolates were not the same, except for two from the same laboratory where the source of pestivirus contamination may have been common.

Animals↗

Prevalence of antibody to caprine arthritis-encephalitis virus in goats in the United States.

Goats from 28 states were tested for antibodies to caprine arthritis-encephalitis virus. Of 3,790 goats, 1,175 (31%) tested positive, and of 196 herds tested, 143 (73%) had 1 or more seropositive members. This prevalence, based on serum samples from all goats in the participating herds, was lower than most rates reported in other studies. Such studies were based on fewer samples, incomplete sampling of herds, or smaller geographic base. Prevalence was highest in western Pacific and northern plains regions, increased with age to 3 years, was highest among goats on family-owned farms, and was lowest in the Angora breed. Differences in prevalence was not related to gender or size of herd.

Animals↗

Evaluation of an enzyme-linked immunosorbent assay for the detection of antibodies to caprine arthritis-encephalitis virus in goat serum.

An indirect enzyme-linked immunosorbent assay (ELISA), was evaluated for its ability to detect serum antibodies against caprine arthritis-encephalitis virus (CAEV). The ELISA was compared to three other serological immunoassays, agar gel immunodiffusion test (AGIDT), immunoblot assay (IBA), and a fixed-cell immunoperoxidase assay (FCIPA). A total of 511 samples, from 40 farms representing a variety of goat breeds and ages were tested. An estimate of the ELISA sensitivity and specificity was made, relative to combined test results of the three other CAEV serological assays. The degree of agreement of test results among these four assays was evaluated. The number of positives detected by the ELISA, AGIDT, IBA and IPA tests was 193, 154, 204 and 163, respectively. Of the 511 sera tested, 172 were positive to any two or all three of these tests, and were defined as reference positive. A total of 237 samples were negative to all three reference tests, and were defined as reference negative. Relative to these references, the ELISA had a point estimate of 98.3% sensitivity and 97.9% specificity. There was good agreement between the ELISA and the other three assays with a kappa statistic of agreement greater than 0.7 for all three comparisons. The ELISA is therefore considered a suitable assay, with high sensitivity and specificity, for detection of antibodies to CAEV in serum.

Animals↗

Cohort study of natural transmission and two methods for control of caprine arthritis-encephalitis virus infection in goats on a California dairy.

A prospective observational cohort study of 361 dairy goat kids was conducted to compare 2 methods of controlling caprine arthritis-encephalitis virus infection under commercial dairy conditions. To compare effectiveness of feeding kids pasteurized milk vs serologic testing and segregation in addition to pasteurized milk feeding, goats were monitored up to the age of 30 months by use of monthly agar gel immunodiffusion testing. Survival analysis methods were used to determine whether age at seroconversion differed between the 2 groups. Significantly lower rates of seroconversion were observed in the segregated group (P < 0.001), compared with the nonsegregated group. Of 193 goats in the pasteurized milk-only group, 146 (75.6%) seroconverted within the 30-month study period, whereas infection was detected in 39 (23.2%) of 168 goats in the test/segregated group. Nonsegregated goats were 3.37 times more likely to seroconvert by 24 months of age, and 70.3% of seroconversions by 24 months of age could be attributed to nonsegregation. For age-specific intervals beyond 180 days of age, 70 to 100% of seroconversions could be attributed to lack of segregation. Cohort life tables for age at seroconversion were reported for each group. Type of colostrum fed, sex, and weaning group (season) were not significantly associated with age at seroconversion. Saanen goats had lower age-specific risk of seroconversion in the nonsegregated group alone and overall. Non-Saanen goats wee 1.5 times more likely to seroconvert than were Saanen goats, when adjusted for a possible confounding effect of weaning group. Results indicate that pasteurized milk feeding and routine test and segregation would be a substantially more effective means of control of the disease in dairy goat herds than would pasteurized milk feeding alone.

Age Factors↗

Genomic heterogeneity of small ruminant lentiviruses detected by PCR.

In order to detect a large spectrum of small ruminant lentiviruses, primers for PCR were chosen in conserved parts of the LTR and GAG genes of Icelandic Visna virus 1514 and of the POL gene of caprine arthritis-encephalitis virus. This set of primers was tested in six different caprine arthritis-encephalitis virus (CAEV)- and Maedi-Visna virus isolates of Dutch, American and Swiss origin. The LTR primers allowed the detection of the corresponding fragments of all isolates. The GAG primers allowed amplification of the corresponding fragments of all but the Swiss Maedi-Visna virus strain OLV. Using the POL primers, one Maedi-Visna- and two caprine arthritis-encephalitis virus strains were detected after one round of amplification. Sequencing of the GAG and POL amplification products and comparison to Icelandic Visna virus and CAEV strain CO revealed total heterogeneity of 38% for the GAG- and 28% for the POL fragment. The virus strains studied fall into two groups which are more closely related to one another than to Icelandic Visna virus.

Amino Acid Sequence↗

Neutralization-resistant antigenic variants of caprine arthritis-encephalitis lentivirus associated with progressive arthritis.

Fifteen newborn Saanen goats were orally infected with a biologically cloned isolate of caprine arthritis-encephalitis virus (CAEV-63). At 33.5 months after infection, 8 of 12 seropositive goats had CAEV-63-specific neutralizing antibody. Five neutralization-positive goats developed clinically apparent arthritis of carpal joints, three of which had periarticular swelling indicating severe synovitis. Arthritis was not evident in age-matched controls or infected goats without neutralizing antibody. Multiple viral isolates were obtained from synovial fluid or synovial fluid cells of arthritic joints between 36.4 and 44.9 months after infection, and successive isolates from individual joints were defined as antigenic variants expressing type-specific neutralization epitopes. Thus, the evolution of neutralizing antibody does not arrest viral replication or development of progressive inflammatory lesions. Rather, some antigenic variants produced in the presence of neutralizing antibody are clonally expanded within carpal joints, and severe joint inflammation is specifically associated with these variants.

Animals↗

Structure and genetic variability of envelope glycoproteins of two antigenic variants of caprine arthritis-encephalitis lentivirus.

To define the structure of the caprine arthritis-encephalitis virus (CAEV) env gene and characterize genetic changes which occur during antigenic variation, we sequenced the env genes of CAEV-63 and CAEV-Co, two antigenic variants of CAEV defined by serum neutralization. The deduced primary translation product of the CAEV env gene consists of a 60- to 80-amino-acid signal peptide followed by an amino-terminal surface protein (SU) and a carboxy-terminal transmembrane protein (TM) separated by an Arg-Lys-Lys-Arg cleavage site. The signal peptide cleavage site was verified by amino-terminal amino acid sequencing of native CAEV-63 SU. In addition, immunoprecipitation of [35S]methionine-labeled CAEV-63 proteins by sera from goats immunized with recombinant vaccinia virus expressing the CAEV-63 env gene confirmed that antibodies induced by env-encoded recombinant proteins react specifically with native virion SU and TM. The env genes of CAEV-63 and CAEV-Co encode 28 conserved cysteines and 25 conserved potential N-linked glycosylation sites. Nucleotide sequence variability results in 62 amino acid changes and one deletion within the SU and 34 amino acid changes within the TM.

Amino Acid Sequence↗

Mononuclear phagocytes as targets, tissue reservoirs, and immunoregulatory cells in human immunodeficiency virus disease.

We have presented evidence in this review for the following: 1. Macrophages are likely the first cell infected by HIV. Studies document recovery of HIV into macrophages in the early stages of infection in which virus isolation in T cells is unsuccessful and detectable levels of antibodies against HIV are absent. 2. Macrophages are major tissue reservoirs for HIV during all stages of infection. Unlike the lytic infection of T cells, many HIV-infected macrophages show little or no virus-induced cytopathic effects. HIV-infected macrophages persist in tissue for extended periods of time (months) with large numbers of infectious particles contained within intracytoplasmic vacuoles. 3. Macrophages are a vector for the spread of infection to different tissues within the patient and between individuals. Several studies suggest a "Trojan horse" role for HIV-infected macrophages in dissemination of infectious particles. The predominant cell in most bodily fluids (alveolar fluid, colostrum, semen, vaginal secretions) is the macrophage. In semen, for example, the numbers of macrophages exceed those of lymphocytes by more than 20-fold (Wolf and Anderson 1988). 4. Macrophages are major regulatory cells that control the pace and intensity of disease progression in HIV infection. Macrophage secretory products are implicated in the pathogenesis of CNS disease and in control of viral latency in HIV-infected T cells. This litany of events in which macrophages participate in HIV infection in man parallels similar observations in such animal lentivirus infections as visna-maedi or caprine arthritis-encephalitis viruses. HIV interacts with monocytes differently than with T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention.

Antigens, Differentiation, Myelomonocytic↗

Transmembrane protein oligomers of caprine arthritis-encephalitis lentivirus are immunodominant in goats with progressive arthritis.

To dissect mechanisms of caprine arthritis-encephalitis lentivirus-induced arthritis, an undefined immunodominant viral glycoprotein, gp90 (G. C. Johnson, A. F. Barbet, P. Klevjer-Anderson, and T. C. McGuire, Infect. Immun. 41:657-665, 1983), was characterized. Monoclonal antibody to gp90 and specific antiserum to env gene products demonstrated that gp90 was a transmembrane protein (TM) dimer. Goats with progressive arthritis had high antibody titers to oligomeric and monomeric (38-kDa) TM.

Animals↗

rev-like transcripts of caprine arthritis encephalitis virus.

The pattern of expression of the caprine arthritis encephalitis virus genome (CAEV) in acutely infected tahr lung cells was found to be complex and temporally regulated. Employing Northern analysis, five CAEV-specific transcripts, 9, 6.5, 5.0, 2.5, and 1.4 kb, were detected. Nucleotide sequence analysis established the genetic structure of two species of cDNA, isolated from a library of CAEV-infected tahr cells, and suggested that they represent rev-like transcripts. One of these cDNA species was composed of three exons--the leader, an exon derived from the 5' region of env, and an exon which spanned the 3' orf. The second cDNA species consisted of four exons--three of which were identical with those of the former species. The additional exon (the second) was located at the 3' end of pol. These transcripts could potentially encode three proteins--a Rev-like protein, which is a fusion of 38 amino acids derived from the N-terminus of env and 91 residues from the 3' orf; a truncated form of the env transmembrane protein, and a novel protein, designated X composed of 73 amino acids. Thus, CAEV, like other lentiviruses, displays a complex pattern of gene expression, characterized by alternative splicing and the production of potentially polycistronic transcripts.

Amino Acid Sequence↗

Defective viral particles in caprine arthritis encephalitis virus infection.

Attempts to isolate full-length unintegrated circular forms of the caprine arthritis encephalitis virus (CAEV) genome yielded only a large number of molecules with deletions. The 3' borders of most of these deletions were near the U3 region of the long terminal repeat whereas the 5' edges were found at various upstream sites within pol or env. With one exception, gag sequences were always present. Analysis of molecular clones derived from integrated proviral CAEV genomes from the same infected cells showed a similar spectrum of deletions. The presence of transcriptionally active elements within the U3 domain of the defective genomes, as well as cis-acting elements within the leader sequences known to be required for efficient encapsidation of viral RNA, suggested that the defective viral DNA genomes could be transcribed into defective RNA molecules which could then be packaged into virions. Isopycnic density gradient centrifugation of supernatants of infected cell cultures indicated the presence of particles with densities less than that expected for intact virions (1.16 g/cc). Northern analysis revealed the presence of smaller viral-specific RNAs that lacked env sequences. These data, along with the structures of the molecular clones, suggest that CAEV stocks contain particles with defective genomes. The role of these particles in influencing the course of virus infection remains to be determined.

Animals↗

Lentiviral arthritis and encephalitis in goats in north-west Syria.

A survey for antibodies against caprine arthritis and encephalitis (CAE) virus was undertaken in north-west Syria. Out of 72 sera, using agar immuno-diffusion test, 12.5% showed a positive reaction. Despite the seropositiveness, no clinical evidence of the infection was found in the tested animals. The findings indicate that the infection is endemic in the area studied.

Animals↗

Lessons from caprine and ovine retrovirus infections.

Two lentiviruses that infect sheep and goats have been shown to be closely related to the human immunodeficiency virus (HIV). These ungulate lentiviruses cause a spectrum of diseases, including arthritis in their natural hosts. The molecular and cellular biology of these viruses as well as possible pathogenic mechanisms is compared to HIV-1 in order to identify common features and significant differences between the human and animals pathogens.

Animals↗