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The complete surface glycoprotein (SU) nucleotide sequences of three French isolates of caprine arthritisencephalitis virus (CAEV) were determined and compared with those of previously described isolates: three American isolates and one French isolate. Phylogenetic analyses revealed the existence of four distinct and roughly equidistant evolutionary CAEV subtypes. Four conserved and five variable domains were identified in the SU. The fine specificities of antibodies produced against these domains during natural infection were examined using a pepscan analysis. Nine immunogenic segments were delineated throughout the conserved and variable domains of SU, two of them corresponding to conserved immunodominant epitopes. Antigenic determinants which may be involved in the immunopathogenic process induced by CAEV were identified. These results also provide sensitive and specific antigen peptides for the serological detection and differentiation of CAEV and visna/maedi virus infections.The surface glycoprotein (SU) of lentiviruses contains determinants important for cellular host range, infectivity, cytopathogenicity, and disease progression. The region of the envelope gene encoding the SU displays a particularly high level of sequence variation, resulting in hypervariable domains interspersed with less variable domains throughout the protein. Both variable and conserved domains are major targets for the host immune response, including virus-neutralizing antibodies and cell-mediated cytotoxicity. Therefore, SU has been an obvious candidate in vaccine trials and diagnostic assays of infection by lentiviruses, such as human, simian, and feline immunodeficiency viruses (HIV, SIV, and FIV, respectively) (for reviews, see references 10, 19, 33, 34, and 38).Caprine arthritis-encephalitis virus (CAEV) is a lentivirus causing slow and persistent inflammatory diseases in goats, primarily arthritis and mastitis (9, 42). These inflammatory diseases are the result of viral infection of cells of monocyte/ macrophage lineage, which are the main target cells in vivo (13,43,44). The results of a recent experiment using live attenuated CAEV vaccine in goats have demonstrated the development of some protection against challenge with the pathogenic homologous virus (17), indicating the effectiveness of an immunological control of virus replication. However, this protective immunity did not prevent the development of clinical signs of disease, although the lesions were not as severe as those found in wild-type CAEV-infected goats. Previous investigations have indicated that the presence and severity of arthritic lesions are specifically correlated with the predominant humoral immune response directed against the SU and transmembrane (TM) CAEV envelope glycoproteins (3,22,30,35). Collateral experiments have demonstrated that infected goats having early dominant anti-SU antibody responses (48) as well as goats challenged with CAEV during persistent CAEV infection or after vaccination with inactivated virus (37) developed more rapidly progr...

The full extent of genetic diversity among small ruminant lentiviruses (SRLVs), i.e., caprine arthritis encephalitis viruses (CAEVs) and maedi-visna viruses (MVVs), remains unknown. This is due in part to the fact that few sequences of CAEV are available. To contribute to this knowledge, gag, pol, and env nucleotide sequences from an SRLV named CA680 originating from a goat from western France were determined. This analysis revealed that this virus is closely related to the Cork and 63 CAEV American isolates. Mismatched amino acids between the CA680 virus and prototype CAEVs ranged from 6.7, 0. 7, and 17.5% for gag, pol, and SU sequences, respectively. The differences between the CA680 virus and MVV prototypes ranged from 16.5, 12.5, and 32.3% for the protein sequences, respectively. A screening using a heteroduplex mobility assay (HMA) adapted to SRLVs revealed that 6 of 10 caprine virus field isolates were closely related to CA680, indicating that this latter isolate was a prototype of CAEVs common in the west of France. Phylogenetic trees drawn using CA, RT, or SU sequences of numerous SRLVs and rooted with EIAV sequences revealed that CA680 and CAEV prototypes, all infectious for goat, clustered in one group. From these HMA and phylogenetic analyses, it appears that U.S. and French caprine SRLVs form a clade that had emerged from a much more diverse group containing all SRLVs infectious for sheep. These ovine SRLVs form a more ancient group in which the EIAV is rooted.