Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to disease
Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to disease
复制标题
围产期感染婴儿中 1 型人类免疫缺陷病毒的演变，疾病进展快速和缓慢
作者：
Francesca Salvatori;S. Masiero;C. Giaquinto;Christopher M. Wade;A. J. L. Brown;L. Chieco;A. D. Rossi
我们研究了人类免疫缺陷病毒1型（HIV-1）变异的起源和进化与围产期感染婴儿疾病结局之间的关系，方法是研究从5名分娩时传播病毒的母亲获得的样本中病毒变异的V3区域，并在出生后一年内依次从其感染婴儿中获得，其中2名（快速进展者）迅速发展为艾滋病。系统发育分析表明，母子对的V3序列聚集在一起，与其他母子对的V3序列明显不同。在每一对中，儿童的序列形成一个单系组，表明在快速和缓慢的进展中，一个单一的变异启动了感染。所有5名婴儿的血浆HIV-1 RNA水平在出生后的头几个月都有所上升，只有3名进展缓慢的婴儿在出生后的第一个学期内有所下降。所有婴儿的V3变异都随着时间的推移而增加，但就潜在的病毒表型而言，V3进化模式没有观察到差异。同义和非同义替换的数量在生命的第一个学期发生变化，与病毒载量、CD4+细胞计数和疾病进展无关。相反，在生命的第二阶段，慢进度虫的非同义替换率高于同义替换率，而快进度虫的非同义替换率则高于慢进度虫，这表明前者的宿主选择压力更大。鉴于V3基因进化主要受宿主免疫约束的提议，这些发现表明，尽管V3的免疫反应可能有助于调节生命第一学期后的病毒水平，但它不太可能在出生后不久的初始病毒下降中发挥决定性作用。
We addressed the relationship between the origin and evolution of human immunodeficiency virus type 1 (HIV-1) variants and disease outcome in perinatally infected infants by studying the V3 regions of viral variants in samples obtained from five transmitting mothers at delivery and obtained sequentially over the first year of life from their infected infants, two of whom (rapid progressors) rapidly progressed to having AIDS. Phylogenetic analyses disclosed that the V3 sequences from each mother-infant pair clustered together and were clearly distinct from those of the other pairs. Within each pair, the child's sequences formed a monophyletic group, indicating that a single variant initiated the infection in both rapid and slow progressors. Plasma HIV-1 RNA levels increased in all five infants during their first months of life and then declined within the first semester of life only in the three slow progressors. V3 variability increased over time in all infants, but no differences in the pattern of V3 evolution in terms of potential viral phenotype were observed. The numbers of synonymous and nonsynonymous substitutions varied during the first semester of life regardless of viral load, CD4+-cell count, and disease progression. Conversely, during the second semester of life the rate of nonsynonymous substitutions was higher than that of synonymous substitutions in the slow progressors but not in the rapid progressors, thus suggesting a stronger host selective pressure in the former. In view of the proposal that V3 genetic evolution is driven mainly by host immune constraints, these findings suggest that while the immune response to V3 might contribute to regulating viral levels after the first semester of life, it is unlikely to play a determinant role in the initial viral decline soon after birth.
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人类免疫缺陷病毒载量的快速增加与垂直感染婴儿的早期疾病进展和 CD4 细胞丧失相关。
DOI：
10.1093/infdis/170.5.1279
发表时间：
1994
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Dickover,RE;Dillon,M;Gillette,SG;Deveikis,A;Keller,M;Plaeger-Marshall,S;Chen,I;Diagne,A;Stiehm,ER;Bryson,Y
通讯作者：
Bryson,Y
影响因子：
56.9
作者：
WOLINSKY, SM;WIKE, CM;MUNOZ, JL
通讯作者：
MUNOZ, JL
DOI：
10.1073/pnas.85.9.3198
发表时间：
1988-05
影响因子：
11.1
作者：
James R. Rusche;K. Javaherian;Charlene MCDANALt;J. Petro;Debra L. Lynn;R. Grimaila;Alphonse J. LANGLOISt;Robert C. Gallo;P. Fischinger;Dani P. BOLOGNESIt;SCOTr D. Putney;Thomas J. MATTHEWSt
通讯作者：
James R. Rusche;K. Javaherian;Charlene MCDANALt;J. Petro;Debra L. Lynn;R. Grimaila;Alphonse J. LANGLOISt;Robert C. Gallo;P. Fischinger;Dani P. BOLOGNESIt;SCOTr D. Putney;Thomas J. MATTHEWSt
影响因子：
56.9
作者：
PIATAK, M;SAAG, MS;LIFSON, JD
通讯作者：
LIFSON, JD
HIV-1 gp120 第三个可变环的一个区域被来自两名急性血清转化患者的 HLA-B7 限制性 CTL 识别。
DOI：
--
发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Safrit,JT;Lee,AY;Andrews,CA;Koup,RA
通讯作者：
Koup,RA