University of California San Diego, La Jolla, California 92093-0679, USA.
J Med Virol. 2012 Nov;84(11):1703-9. doi: 10.1002/jmv.23398.
The genital tract of individuals infected with human immunodeficiency virus type 1 (HIV-1) is an anatomic compartment that supports local HIV-1 and cytomegalovirus (CMV) replication. This study investigated the association of seminal CMV replication with changes in HIV-1 clonal expansion, evolution and phylogenetic compartmentalization between blood and semen. Fourteen paired blood and semen samples were analyzed from four untreated subjects. Clonal sequences (n = 607) were generated from extracted HIV-1 RNA (env C2-V3 region), and HIV-1 and CMV levels were measured in the seminal plasma by real-time PCR. Sequence alignments were evaluated for: (i) viral compartmentalization between semen and blood samples using Slatkin-Maddison and F(ST) methods, (ii) different nucleotide substitution rates in semen and blood, and (iii) association between proportions of clonal HIV-1 sequences in each compartment and seminal CMV levels. Half of the semen samples had detectable CMV DNA, with at least one CMV positive sample for each patient. Seminal CMV DNA levels correlated positively with seminal HIV-1 RNA levels (Spearman P = 0.05). A trend towards an association between compartmentalization of HIV-1 sequences sampled from blood and semen and presence of seminal CMV was observed (Cochran Q test P = 0.12). Evolutionary rates between semen and blood HIV-1 populations did not differ significantly, and there was no significant association between seminal CMV DNA levels and the frequency of non-unique clonal HIV-1 sequences in the semen. In conclusion, the effects of CMV replication on HIV-1 viral and immunologic dynamics within the male genital tract are not significant enough to perturb evolution or disrupt compartmentalization in the genital tract.
受人类免疫缺陷病毒 1 型（HIV-1）感染的个体的生殖道是一个解剖部位，支持局部 HIV-1 和巨细胞病毒（CMV）复制。本研究调查了精液 CMV 复制与 HIV-1 克隆扩展、进化和血液与精液之间的系统发生区室化变化之间的关联。对来自四个未经治疗的个体的 14 对血液和精液样本进行了分析。从提取的 HIV-1 RNA（env C2-V3 区）生成克隆序列（n=607），并通过实时 PCR 测量精液中的 HIV-1 和 CMV 水平。序列比对评估了以下内容：（i）使用 Slatkin-Maddison 和 F(ST) 方法评估精液和血液样本之间的病毒区室化，（ii）精液和血液中不同的核苷酸替代率，以及（iii）每个区室中克隆 HIV-1 序列的比例与精液 CMV 水平之间的关联。一半的精液样本可检测到 CMV DNA，每个患者至少有一个 CMV 阳性样本。精液 CMV DNA 水平与精液中 HIV-1 RNA 水平呈正相关（Spearman P=0.05）。观察到从血液和精液中采样的 HIV-1 序列的区室化与精液 CMV 存在之间存在关联的趋势（Cochran Q 检验 P=0.12）。精液和血液 HIV-1 群体之间的进化率没有显著差异，精液 CMV DNA 水平与精液中非独特克隆 HIV-1 序列的频率之间也没有显著关联。总之，CMV 复制对男性生殖道内 HIV-1 病毒和免疫动力学的影响不足以扰乱进化或破坏区室化。
