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Up‐regulation of β‐chemokines and down‐modulation of CCR5 co‐receptors inhibit simian immunodeficiency virus transmission in non‐human primates
Author(s) -
Lehner T.,
Wang Y.,
Cranage M.,
Tao L.,
Mitchell E.,
Bravery C.,
Doyle C.,
Pratt K.,
Hall G.,
Dennis M.,
Villinger L.,
Bergmeier L.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00993.x
Subject(s) - simian immunodeficiency virus , biology , chemokine , macrophage inflammatory protein , virology , cd8 , immunology , chemokine receptor , receptor , in vivo , virus , immune system , biochemistry , microbiology and biotechnology
Summary A non‐cognate mechanism of protection against human immunodeficiency virus‐1 (HIV‐1) infection involves up‐regulation of β‐chemokines, which bind and may down‐modulate the CCR5 co‐receptors, thereby preventing transmission of M‐tropic HIV‐1. The objective of this investigation was to evaluate this mechanism in vivo in non‐human primates. Rhesus macaques were immunized by a modified targeted lymph nodes (TLN) route with recombinant simian immunodeficiency virus (SIV) glycoprotein 120 (gp120) and p27 in alum, and adsorbed recombinant granulocyte–macrophage colony‐stimulating factor (GM‐CSF) with either interleukin (IL)‐2 or IL‐4. Immunization induced significant increases in the concentrations of CD8 cell‐derived suppressor factor (CD8‐SF), regulated on activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)‐1α and MIP‐1β, and down‐modulation of the proportion of cells expressing CCR5 ( r = 0·737, P < 0·05). The macaques were then challenged with SIVmac 220 by the rectal mucosal route. The plasma SIVmac RNA showed a significant inverse correlation with the CD8‐SF or the concentration of the three β‐chemokines ( r = 0·831 and 0·824, P < 0·01), but a positive correlation between the proportion of CCR5 + cells and SIVmac RNA ( r = 0·613, P = 0·05). These results demonstrate for the first time in vivo that immunization up‐regulates β‐chemokines, which may down‐modulate CCR5 co‐receptors, and both functions are significantly correlated with the viral load. Hence, the non‐cognate β‐chemokine–CCR5 mechanism should be considered as complementary to specific immunity in vaccination against HIV.