title: Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef.
abstract: 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.
authors: The Kansas University of Medical Center, MMD Laboratory of Viral Pathogenesis, Kansas City, KS 66160, USA.
authors: Baya Amel
authors: BA
authors: Bouzar
authors: Angela
authors: A
authors: Rea
authors: Stephanie
authors: S
authors: Hoc-Villet
authors: Céline
authors: C
authors: Garnier
authors: François
authors: F
authors: Guiguen
authors: Yuhuai
authors: Y
authors: Jin
authors: Opendra
authors: O
authors: Narayan
authors: Yahia
authors: Y
authors: Chebloune
mesh_terms: D000818:Animals; D017209:Apoptosis; D016088:Arthritis-Encephalitis Virus, Caprine / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D001483:Base Sequence; D049109:Cell Proliferation; D002678:Chimera / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006041:Goats; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008264:Macrophages / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins