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 pathogenic SIV(mac251) and SIV(SME660) by the mucosal route, were used in a pilot study to investigate whether infectability of ex vivo lymph nodes could predict resistance and/or susceptibility to SIV infection in vivo. Of six macaques exposed to the less-pathogenic virus SIV(MNE), four resisted viral infection. Analysis of the susceptibility of the PBMC of these four animals before SIV(MNE) challenge indicated that all of them were resistant to infection by the SIV(BK28) isolate and, in three of them, this resistance was dependent on CD8+ T cells. Blocks of lymph nodes of these four macaques were resistant to SIV(MNE) infection ex vivo following SIV(MNE) viral challenge exposure. However, the same blocks from the same animals were permissive to the more virulent SIV(251(32H)). Accordingly, three of these macaques were readily infected following challenge exposure with SIV(251(32H)). Lymphoproliferative responses 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 infection. 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 in vivo infection.
Margolis
L
L
Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Glushakova
S
S
Chougnet
C
C
Shearer
G
G
Markham
P
P
Robert-Guroff
M
M
Benveniste
R
R
Miller
C J
CJ
Cranage
M
M
Hirsch
V
V
Franchini
G
G
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D019742:Chemokines, CC / Q000378:metabolism; D046508:Culture Techniques; D004198:Disease Susceptibility; D015686:Gene Products, env / Q000097:blood / Q000378:metabolism; D015683:Gene Products, gag / Q000097:blood / Q000378:metabolism; D015693:Gene Products, nef / Q000097:blood / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000821:virology*; D008251:Macaca; D010865:Pilot Projects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity*; D014779:Virus Replication
D019742:Chemokines, CC; C066594:Gag protein p27, Simian immunodeficiency virus; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef