10例长期感染1型人免疫缺陷病毒患者的病毒和免疫学特征分析

Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection

约有5%～8%的Ⅰ型人免疫缺陷病毒(HIV-Ⅰ)感染者可以无症状地生存15年以上,这些感染者的 HIV-Ⅰ病毒与一般的 HIV-Ⅰ有何异样?这些感染者机体的免疫状态有何特征?我们对10例感染 HIV-Ⅰ后的长期生存者体内病毒和机体的免疫能力进行检测,发现这些病人体内的 HIV-Ⅰ很可能是减弱病毒,而他们体内对抗 HIV-Ⅰ的免疫能力相对强。

We have studied 10 long-term non-progressors who are asymptomatic with normal and stable CD4^+ lymphocyte counts despite 12 to 16 years of HIV-1 infection.Multiple methods were used to determine the viral load in their blood.Plasma culturs were uniformly negative for infectious virus.However,particle associated HIV-1 RNA was detectable in 4 subjects using a sensitive branched DNA amplification assay,with values ranging from 839 to 11,549 copies/ml.Five other subjects had levels below 630 RNA copies/ml.In peripheral blood mononuclear cells(PBMC),infectious HIV-1 was detected and quantified(50,5,and 0.2 TC1D50/10~6 cells)in 3 subjects using a standard limiting-dilution culture method.Infectious virus was recovered from another subject us- ing a CD8-depleted culture.In contrast,6 subjects had no detectable infectious virus in PBMC(<0.1 TCID50/10~6cells).All had detectable viral DNA in PBMC by a quantitative polymerase chain reaction assay,but the copy numbers were low,ranging from 10 to 100 copies/10~6PBMC in all but 2 subjects.Overall,the viral bur- den in the plasma and PBMC of long-term survivors was orders of magnitude lower than those typically found in progressors. Possible mechanisms for low levels of HIV-1 in vivo were examined experimentally.No evidence for resistance of host CD4^+ lymphocytes to HIV-1 infection was found.In contrast,long-term survivors exhibited a vigorous vi- rus-inhibitory,CD8^+ lymphocte response,concomitantly with a strong neutralizing antibody response.Moreover, in 2 subjects,attenuation of HIV-1 was evident on the basis of poor viral replication kinetics in vitro. Our finding suggests that non-progression appears to be associated with low levels of HIV-1 in the presence of a combination of strong virus-specific immune responses and some degree of viral attenuation.The level of virus and the degree of immunity observed in long-term survivors could also serve as guideposts for our therapeutic and prophylactic efforts against AIDS.