Wang Yufei, Bergmeier Lesley A, Stebbings Richard, Seidl Thomas, Whittall Trevor, Singh Mahavir, Berry Neil, Almond Neil, Lehner Thomas
Kings College London at Guy's Hospital, London SE1 9RT, England, UK.
Vaccine. 2009 Feb 5;27(6):870-81. doi: 10.1016/j.vaccine.2008.11.084. Epub 2008 Dec 11.
APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p< or =0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4(+)CCR5(+) memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4(+)CCR5(+) circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5(+)CD4(+) memory and CD4(+)CD95(+)CCR7(-) effector memory T cells.
载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G）是一种先天性细胞内抗病毒因子，可将逆转录病毒的胞嘧啶脱氨基为尿嘧啶。在用与70kDa热休克蛋白连接的SIV抗原和CCR5肽进行粘膜免疫后，在恒河猴体内进行了APOBEC3G（A3G）的体内研究。每次免疫后外周血单核细胞（PBMC）中A3G mRNA逐渐增加（p<0.0002至p<或=0.02），并维持至少17周。记忆T细胞分析显示，与未免疫的猕猴相比，免疫猕猴循环（p=0.0001）、脾脏（p=0.0001）、髂淋巴结（p=0.002）和直肠（p=0.01）细胞中CD4(+)CCR5(+)记忆T细胞中的A3G mRNA和蛋白显著增加。用SIVmac 251进行粘膜攻击显示，在免疫未感染的猕猴中，CD4(+)CCR5(+)循环细胞（p<0.01）和引流髂淋巴结细胞（p<0.05）中的A3G mRNA显著增加，这与A3G发挥的保护作用一致。结果表明，在非人类灵长类动物中进行粘膜免疫可诱导CCR5(+)CD4(+)记忆和CD4(+)CD95(+)CCR7(-)效应记忆T细胞对先天性抗病毒因子的记忆反应特征。
