Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef
- Kansas University of Medical Center, MMD Laboratory of Viral Pathogenesis, 5000 Wahl Hall East, 3901 Rainbow Blvd. Kansas City, Kansas 66160 (United States)
- UMR 754 INRA, 'Virologie Cellulaire, Moleculaire et Maladies Emergentes', Universite Claude Bernard Lyon-1, Batiment B, 50 avenue Tony Garnier, 69007, Lyon (France)
- UMR 754 INRA, 'Virologie Cellulaire, Moleculaire et Maladies Emergentes', Universite Claude Bernard Lyon-1, Batiment B, 50 avenue Tony Garnier, 69007, Lyon (France) and Kansas University of Medical Center, MMD Laboratory of Viral Pathogenesis, 5000 Wahl Hall East, 3901 Rainbow Blvd. Kansas City, Kansas 66160 (United States)
Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats, well known for its tropism for macrophages and its inability to cause infection in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To test the hypothesis that when nef is expressed by the viral genome, the virus became toxic for lymphocytes during replication in macrophages, we inserted the SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV-nef. This recombinant virus is not infectious for lymphocytes but is fully replication competent in goat macrophages in which it constitutively expresses the SIV Nef. We found that goat lymphocytes cocultured with CAEV-nef-infected macrophages became activated, showing increased expression of the interleukin-2 receptor (IL-2R). Activation correlated with increased proliferation of the cells. Interestingly, a dual effect in terms of apoptosis regulation was observed in exposed goat lymphocytes. Nef was found first to induce a protection of lymphocytes from apoptosis during the first few days following exposure to infected macrophages, but later it induced increased apoptosis in the activated lymphocytes. This new recombinant virus provides a model to study the functions of Nef in the context of infection of macrophages, but in absence of infection of T lymphocytes and brings new insights into the biological effects of Nef on lymphocytes.
- OSTI ID:
- 20977044
- Journal Information:
- Virology, Vol. 364, Issue 2; Other Information: DOI: 10.1016/j.virol.2007.02.032; PII: S0042-6822(07)00137-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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