中国科学院昆明动物研究所机构知识库

中缅边境地区毗邻“金三角”地区，是毒品运输的重要枢纽，已成为HIV-1重组的热点地区。HIV-1 B亚型、C亚型和流行重组型（Circulating recombinant forms, CRF）01_AE在20世纪80年代跨境传播至中缅边境地区，其共同流行促进了大量重组毒株（Recombinant form, RF）的出现和流行。CRF07_BC和CRF08_BC在20世纪90年代初形成于我国云南省，随后迅速扩散至全国其它省份，成为中国的主要流行株。实验室前期工作表明：缅甸北部克钦邦的静脉注射吸毒人群（Injecting drug users, IDUs）中，HIV-1重组毒株的流行比例已高达86.1%；另外，跨中缅边境缅甸籍长途卡车司机能双向传播HIV-1。HIV-1在中缅边境的传播日益复杂，然而IDUs对该地区HIV-1的传播作用却不甚清楚。为探讨IDUs在HIV-1跨中缅边境传播中的作用，本论文对2010-2013年旅居云南省德宏州陇川县、盈江县和瑞丽市的缅甸籍静脉注射吸毒人群（Burmese injecting drug users in Yunnan, BIDUY）进行HIV-1检测、系统进化和系统地理学分析。血清学检测结果显示：BIDUY中HIV-1感染率为19.0%（117/617），其中以瑞丽市的感染最为严重（28.4%）。基于HIV-1 p17、pol、vif-env和env基因片段的系统进化分析表明：BC、01_AE/B/C、C、01_AE/C、01_AE、B和01_AE/B流行比例依次为34.1%、27.3%、14.8%、10.2%、9.1%、3.4%和1.1%。基于HIV-1 p17基因片段对B、C和CRF01_AE基因序列进行系统地理学分析，发现中国边境地区HIV-1的最初起源地是缅甸；BIDUY中，大部分HIV-1序列起源于缅甸，少量HIV-1序列起源于德宏；中国德宏的HIV-1序列主要起源于BIDUY，少量序列直接起源于缅甸。以上结果暗示BIDUY更倾向于将HIV-1病毒由缅甸携带至中国。为进一步掌握中缅边境地区HIV-1的新近流行特征，本论文于2013年11月和2014年11月分别对缅甸北部掸邦果敢特区戒毒所和克钦邦迈扎央地区戒毒所的252名和100名吸毒人员进行了流行病学调查。血清学检测结果显示：缅甸北部果敢特区和迈扎央地区吸毒人员的HIV-1感染率分别为12.3%（31/252）、15.0%（15/100）。基于成功扩增的31条HIV-1近乎全长基因组序列（果敢特区26条，迈扎央地区5条）的系统进化分析结果显示：缅甸北部吸毒人群中HIV-1种类多样，包括CRF08_BC、CRF07_BC、CRF01_AE和RFs，尤以后者居多，占87.1%（27/31）；并且，在RFs中，新鉴定出两种新的流行重组型——CRF82_cpx和CRF83_cpx，二者的流行比例分别为19.4%（6/31）和35.5%（11/31），已成为缅甸北部吸毒人群的主要流行株。系统地理学分析结果显示：新鉴定的CRF82_cpx和CRF83_cpx均起源于缅甸，起源时间分别在2002-2006年和2007-2008年。另外，CRF07_BC大约是在1996年由中国的新疆传播至缅甸北部的，而CRF08_BC大约是在1992年由中国的云南省传播至缅甸北部的，本文也是首次发现CRF07_BC和CRF08_BC在中国以外的区域——缅甸北部掸邦果敢特区流行。在缅甸北部暴发流行的CRF82_cpx和CRF83_cpx可能伴随毒品运输、跨境吸毒和跨国商贸等途径扩散至中国云南省，对云南省的HIV-1防控构成一定的威胁。监测中缅边境地区高危人群中HIV-1的流行趋势迫在眉睫。本论文研究结果也能为HIV-1疫苗的设计、HIV-1防控策略的制定以及后期HIV-1的分子流行病研究等提供一定的理论指导。 

As bordering with the “Golden Triangle Region”, the China-Myanmar border region become the crucial transbay of transporting illegal drugs and the hotspots of formatting human immunodeficiency virus type I (HIV-1) recombinants. The cross-border transmission of HIV-1 subtype B, C, and circulating recombinant form (CRF) 01_AE in 1980s lead to the co-circulating of different HIV-1subtypes and the formation of numerous inter-subtype recombinant forms (RFs) in this region. After origin in Yunnan province of China in early 1990s, CRF07_BC and CRF08_BC transmitted to other provinces of China rapidly and became the predominant strains of China. The results of previous studies showed that the proportion of HIV-1 inter-subtype recombinants among injecting drug users (IDUs) in Kachin state of Myanmar was as high as 86.1%; besides, the Burmese long-distance truck drivers who cross China-Myanmar border could transmit HIV-1 in dual-direction. The epidemic pattern of HIV-1 in China-Myanmar border region become more and more complicated; while, the role of transmitting HIV-1 of IDUs in this region are still not clearly described.To explore the role of HIV-1 cross-border transmission that IDUs played in China-Myanmar border region, HIV-1 serological test, phylogenetic analysis and phylogeographical analysis were performed among Burmese IDUs who travelled in Dehong prefecture of Yunnan province (BIDUY) that recruited from 2010 to 2013. Results from serological test showed that the prevalence of HIV-1 among BIDUY was 19.0% (117/617), and Ruili was the most impacted (28.4%, 27/95), respectively. From the phylogenetic analysis that based on HIV-1 p17, pol, vif-env and C2V3 fragments, the HIV-1 subtypes/recombinants among BIDUY were BC (34.1%), 01BC (27.3%), C (14.8%), 01C (10.2%), CRF01_AE (9.1%), B (3.4%) and 01B (1.1%). Based on HIV-1 subtype B, C and CRF01_AE strains of p17 fragment, results of phylogeographical analysis showed that 1) the primary origin of HIV-1 in China-Myanmar border region was Myanmar; 2) Most of the HIV-1 strains of BIDUY were originated from Myanmar, a few of them were originated from Dehong; 3) Most of the HIV-1 strains from Dehong prefecture were originated from BIDUY, only a few of them were originated directly from Myanmar. These results implied that compared to bring HIV-1 strains from China to Myanmar, BIDUY more likely to bring HIV-1 strains from Myanmar to China.To further explore the most recent HIV-1 epidemic characteristics in China-Myanmar border region, molecular epidemiology study of HIV-1 was performed among 252 drug users in the Kokang Autonomous Region of Shan State in November 2013 and 100 drug users in Mai Ja Yang region of Kachin State of Myanmar in November 2014. From the results of HIV-1 serological test, the prevalence of HIV-1 among drug users in Kokang and Mai Ja Yang were 12.3% (31/252) and 15.0% (15/100) respectively. The phylogenetic results based on 31 HIV-1 near full-length genome (26 from Kokang and 5 from Mai Ja Yang) showed that northern Myanmar circulating diverse HIV-1 subtypes, including CRF01_AE, CRF07_BC, CRF08_BC and numerous RFs (87.1%, 27/31). Among these RFs, two new CRFs were identified, which were designated as CRF82_cpx and CRF83_cpx. These two new CRFs accounted for 19.4% (6/31) and 35.5% (11/31) from all amplified sequences, being the predominant strains among drug users in northern Myanmar. Results from phylogeographical analysis showed that both CRF82_cpx and CRF83_cpx most likely originated in Myanmar, and CRF82_cpx originated around 2002-2006 and CRF83_cpx around 2007-2008. Besides, the CRF07_BC strain more likely spread from Xinjiang province of China to Myanmar possibly through Yunnan after 1996, and the CRF08_BC strains spread from Yunnan province to Myanmar after 1992. This is the first report that CRF07_BC and CRF08_BC are circulating outside China, in northern Myanmar.CRF82_cpx and CRF83_cpx that outbreak in northern Myanmar can transmit to Yunnan province of China through illegal drug transport, cross-border drug use and cross-border epitomical activities, being a big threaten to the prevention of HIV-1 in Yunnan, China. Molecular surveillance of HIV-1 among different high risk groups is warranted. Results of this study can also provide some useful references in designing HIV-1 vaccines, drafting HIV-1 prevention strategy and studying HIV-1molecular epidemiology.