Selection of antigenic variants in maedi–visna virus infection

Abstract

In order to analyse the pattern of sequence variation in maedi-visna virus (MVV) in persistently infected sheep and to answer the question of whether antigenic variants are selected in a long-term MVV infection, an 87 bp variable region in the env gene of ten antigenic variants and 24 nonvariants was sequenced. Nine of the ten antigenic variants had mutations in this region, comprising 24 point mutations and a deletion of 3 bp. Twenty-three of the point mutations (96 %) were nonsynonymous. There was only a single mutation in this region in the 24 non-variants. A type-specific neutralizing antibody response appeared in all the sheep 2-5 months post-infection, and in most sheep more broadly reacting neutralizing antibodies appeared up to 4 years later. All the antigenic variants were neutralized by the broadly reacting sera. It is noteworthy that the antigenic variants were isolated at a time when only the type-specific antibodies were acting, before the broadly reacting antibodies appeared. The same picture emerged when molecularly cloned virus was used for infection. Three sheep were infected with a molecularly cloned virus, and of six virus isolates, one was an antigenic variant. This variant arose in the absence of broadly reacting antibodies. The results indicate that there is selection for mutants that escape neutralization. IntroductionMaedi-visna virus (MVV) establishes a lifelong infection of sheep, leading either to progressive meningoencephalomyelitis, characterized by weakness or paralysis of the hind legs (visna) or lung lesions of progressive pneumonia (maedi) (Sigurdsson & Pa! lsson, 1958). MVV is a member of the Lentivirus subfamily of retroviruses, and its primary target cells are considered to be of the monocyte lineage (Gendelman et al., 1986). MVV elicits an immune response in the host, both humoral and cell-mediated (Griffin et al., 1978 ;Larsen et al., 1982 ;Sihvonen, 1981 ;Thormar & Helgado! ttir, 1965 ;Torsteinsdo! ttir et al., 1992), and the persistence of the virus in the face of a strong immune response has long been a puzzle. It has been proposed that one way for the virus to escape the Author for correspondence : Valgerdur Andre! sdo! ttir.Fax j354 5673979. e-mail valand!hi.is †Present address : deCode Genetics, Reykjavı! k, Iceland. ‡Present address : Sigma-Aldrich Fine Chemicals, St Louis, MO 63103, USA.The sequences of the env gene of the three antigenic variants have been submitted to GenBank, accession numbers immune response is by continuous change of epitopes through mutation (Gudnado! ttir, 1974). Antigenic variation has indeed been documented for all lentiviruses (Burns et al., 1993 ;Ellis et al., 1987 ;Gudnado! ttir, 1974 ;Kono et al., 1973 ;McGuire et al., 1988 ;McKeating et al., 1989 ;Montelaro et al., 1984 ;Narayan et al., 1977 ;Siebelink et al., 1993 ;Wolfs et al., 1991), but its significance for pathogenicity has been disputed (Cheevers et al., 1999 ;Lutley et al., 1983 ;Thormar et al., 1983 ;Wolinsky et al., 1996). The envelope genes of the lentiviruses are divided int...

Demonstration of Coinfection with and Recombination by Caprine Arthritis-Encephalitis Virus and Maedi-Visna Virus in Naturally Infected Goats

“…Previous works have estimated the evolution rates of SRLVs in animals infected over the long term (1,12). In light of these results, the large genetic distance observed between the sequence of clone PBMC12-25 in goat 12 and that of clone PBMC13-12 in goat 13 from both cluster I (28.2 and 26%) and cluster II (13.9 and 24.9%) sequences could hardly be attributed to the evolution of these viruses within their hosts.…”

Post-entry blockade of small ruminant lentiviruses by wild ruminants

“…In the last case, host may have evolved to mount an effective long-lasting restriction mechanism of lentiviral replication in vivo. Neutralizing antibodies were detected in ELISA positive sera from red deer however, they unlikely play an important role in the viral infection restrictive pathway as described in caprine and ovine species [ 21 , 50 ]. Serological reaction was mostly detected by home-made ELISA in comparison with commercial tests as described for ovine and caprine infections likely due to the inclusion of novel epitopes providing wider cross-reactivity [ 39 , 51 ].…”

Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View

“…However, the variants usually do not replace the original infecting strain of virus, and the antigenic drift does not appear to be necessary for either virus persistence or development of CNS or lung lesions [292,391]. A recent study, however, showed that there is selection for mutants that escape neutralization [394]. Most viral proteins can act as antigens for CTL, although only epitopes in POL have been characterized in detail [331].…”