Early events in immune evasion by the lentivirus maedi-visna occurring within infected lymphoid tissue

Abstract

Infections caused by lentiviruses, including human immunodeficiency virus, are characterized by slowly progressive disease in the presence of a virus-specific immune response. The earliest events in the vims-host interaction are likely to be important in determining disease establishment and progression, and the kinetics of these early events following lentiviral infection are described here. Lymphatic cannulation in the sheep has been used to monitor both the virus and the immune response in efferent lymph after infection ofthe node with maedi-visna virus (MVV). Viral replication and dissemination could be detected and consisted ofa wave of MW-infected cells leaving the node around 9 to 18 days postinfection. No cell-free virus was recovered despite the fact that soluble MW p25 was detected in lymph plasma. The maximum fiequency of MW-infected cells was ony 11 in 10' but over the first 20 days of infection amounted to greater than 104 virus-infected cells leaving the node. There was a profound increase in the output of activated lymphoblast from the lymph nodes of infected sheep, characterzed by an increased percentage of CD8+ lymphoblasts. All of the CD8+ lymphoblasts at the peak of the response expressed both major histocompatibility complex class H DR and DQ molecules but not interlieukin-2 receptor (CD2S). The in vitro proliferative response ofefferent lymph cells exiting the node after challenge with MVV to both recombinant human interleukin-2 and the mitogen concanavalin A was decreased between days 8 and 16 postinfection, and a

Initial lentivirus-host interactions within lymph nodes: a study of maedi-visna virus infection in sheep

“…Sheep are amenable to surgical lymphatic cannulation, and therefore such a detailed analysis is possible. Previously we have shown that major histocompatibility complex (MHC) class II-positive CD8 ϩ lymphoblasts exit the acutely infected lymph node via efferent lymph at about the same time that low frequencies of virus-infected cells are also detected leaving the node, disseminating the infection (4). It is now appreciated that the lymph nodes are major sites of HIV replication throughout the disease (11,31), and it is therefore likely that the virus-infected cells seen leaving acutely MVV-infected nodes are only a small proportion of the infected cells which remain in the node.…”

Important mammalian veterinary viral immunodiseases and their control

“…The reason(s) for vaccine failure, poor efficacy and the increased disease in some instances remain obscure. An explanation may be stimulation defective T cell responses by the vaccines as suggested to occur during virus infection [54,55]. We believe understanding and countering the defective T cell responses in SRLV infections is important and it may lead eventually to effective vaccines.…”

“…After infection with VMV, sheep mount an antiviral immune response (both antibody and T cell) but viral replication and dissemination still occur. An explanation put forward for this defect in VMV immune response has been the induction CD8+ T lymphocytes in a defective maturation state as also observed in T-cell-tropic lentiviruses [54]. The defective phenotype of CD8+ T lymphocytes in VMV infection involves expression of MHC class II DR and DQ molecules but not interlukin-2 receptor (IL-2R) and hence lacks lymphoproliferative and cytolytic activities [54].…”

“…An explanation put forward for this defect in VMV immune response has been the induction CD8+ T lymphocytes in a defective maturation state as also observed in T-cell-tropic lentiviruses [54]. The defective phenotype of CD8+ T lymphocytes in VMV infection involves expression of MHC class II DR and DQ molecules but not interlukin-2 receptor (IL-2R) and hence lacks lymphoproliferative and cytolytic activities [54]. CD4+ T lymphocytes in VMV infected hosts also appear to be defective and exert a negative influence in the favour of the host.…”

“…In EIAV, VMV, ADV and FIPV there is, as a consequence of the persistent monocyte and macrophage infection, the emergence of viral variants which the immune response fails to clear [4] (and 26-30 (EIAV) and 33-34(SRLV)). In visna/maedi SRLV disease induction of CD8+ T lymphocytes in a defective maturation state (expressing MHC class II DR and DQ molecules but not interleukin-2 receptors) and hence lack lymphoproliferative and cytolytic activities as also observed in infections by primate T lymphocyte-tropic viruses (HIV and SIV) [54] merits further investigation; CD4+ T lymphocytes in SRLV infected hosts also appear to be defective [55]. In monoctye, SRLV infection is latent in that there is no virus transcription and the infected monocyte is neither killed by the virus nor by the host's immune response.…”