人类免疫缺陷病毒-1 CRF01_AE毒株在我国的分子传播网络分析

Molecular transmission networks of human immunodeficiency virus-1 CRF01_AE strains in China

目的构建我国HIV-1 CRF01_AE毒株分子传播网络，并分析网络特征。方法从洛斯阿拉莫斯国家实验室HIV基因数据库（Los Alamos database）下载中国地区的CRF01_AE pol区基因序列并进行人口学信息核对。通过构建系统进化树、提取传播簇、最小基因距离选择及传播网络可视化4个步骤构建传播网络。运用卡方检验分析不同人群参与网络形成的比例和网络中度的分布。描述性分析不同人群和不同地区之间的传播关联。结果2 419条序列共形成250个大小介于2～25的传播网络，包括847个节点和610条边。度≥2的个体虽然只占网络中个体总数的26.4%（224/847），但与66.5%（563/847）的个体存在关联。男男同性性行为者（MSM）、男性异性性行为者、静脉药瘾者（IDUs）及女性异性性行为者参与网络形成的比例分别为37.6%（669/1 781）、28.4%（102/359）、16.1%（10/62）和30.4%（66/217），差异有统计学意义（χ^2＝23.774，P〈0.001）。MSM人群中度≥2的比例（10.8%，193/1 781）显著高于男性异性性行为者（5.6%，20/359）和女性异性性行为者（4.6%，10/217）（P值分别为0.002和0.004）。网络中绝大多数（95.5%，639/669）MSM与其他MSM之间存在传播关联，仅有2.4%（16/669）的个体与女性异性性行为者之间存在传播关联，但有15.1%（10/66）的女性异性性行为者与MSM之间存在传播关联。男性异性性行为者与女性异性性行为者之间存在传播关联的比例为35.3%（36/102），与MSM之间具有传播关联的比例为9.8%（10/102）。网络中20.9%（177/847）的个体与其他省份之间存在传播关联。结论较少比例的超级传播者在CRF01_AE毒株的分子传播网络形成中起到了核心作用，不同人群和不同地区之间的毒株进行着活跃的传播。

Objective To construct the molecular transmission networks of HIV-1 CRF01 _AE strains circulating in China and to analyze their characteristics. Methods Sequences of the pol genes of Chinese CRF01 _AE strains were downloaded from Los Alamos database and the related demographic informa- tion was checked. Transmission networks were created by four steps, including phylogenetic tree construction, transmission cluster extraction, minimum genetic distance identification and network visualization. Chisquare test was performed to analyze the differences in the distribution of different populations in the networks and the differences in the distribution of subjects with different degrees among different sub-populations. Descriptive analysis was used to investigate the transmission links between sub-populations and various regions. Results The 2 419 sequences constituted 250 separate networks including 847 nodes and 610 edges. The number of subjects covered by different networks ranged from 2 to 25. Subjects with degree ≥2 represented only 26.4% （224/847） of network-individuals, but were connected with 66.5 % （563/847） of all network- individuals. There were 37.6% （669/1 781 ） of men who have sex with men （MSM） , 28.4% （102/359） of heterosexual men, 16.1% （10/62） of intravenous drug users （IDUs） and 30.4% （66/217） of heterosexual women involved in the networks （Х^2= 23. 774, P〈0. 001 ）. The percentage of subjects with degree ≥2 was high in MSM （10.8% , 193/1 781 ） compared to that in heterosexual men （5.6%, 20/359） （P= 0.002 ） and heterosexual women （4.6%, 10/217 ） （ P = 0. 004 ）. Of the 669 MSM in the networks, 95.5 % （639/669） linked to other MSM and only 2.4% （16/669） linked to heterosexual women. However, 15.1% （10/66） of the heterosexual women in the networks linked to MSM. Of the heterosexual men in the networks, 35.3% （36/102） linked to heterosexual women, 9.8% （10/102） linked to MSM. Of the subjects in the networks, 20.9% （177/847） linked to other regions＇ individuals. Conclusion The superspreaders played an important role in the molecular transmission networks of HIV-1 CRF01 AE strains even though they were in a minority. The transmission of HIV-1 CRF01 AE strains between sub-populations and various regions was complicated and active.