Replication of simian immunodeficiency virus (SIV) in ex vivo lymph nodes as a means to assess susceptibility of macaques in vivo

Six macaques, apparently uninfected, following low-dose exposure to the pat hogenic SIVmac251 and SIVSME660 by the mucosal route, were used in a pilot study to investigate whether infectability of ex vivo lymph nodes could pre dict resistance and/or susceptibility to SIV infection in vivo. Of six maca ques exposed to the less-pathogenic virus SIVMNE, four resisted viral infec tion. Analysis of the susceptibility of the PBMC of these four animals befo re SIVMNE challenge indicated that all of them were resistant to infection by the SIVBK28 isolate and, in three of them, this resistance was dependent on CD8+ T cells. Blocks of lymph nodes of these four macaques were resista nt to SIVMNE infection ex vivo following SIVMNE viral challenge exposure. H owever, the same blocks from the same animals were permissive to the more v irulent SIV251(32H). Accordingly, three of these macaques were readily infe cted following challenge exposure with SIV251(32H). Lymphoproliferative res ponses in blood or lymph nodes, local C-C chemokine production in the lymph -node explants, and cytotoxic T-cell activity measured throughout the study did not correlate with ex vivo resistance or susceptibility to in vivo inf ection. In conclusion, PBMC and lymph-node resistance or susceptibility to infection ex vivo appeared to correlate with in vivo infectivity and, thus, these approaches should be further tested for their predictive value for i n vivo infection. (C) 2000 Academic Press.