在新加坡,未经治疗的 CRF01_AE 和 CRF51_01B 感染的 HIV-1 患者中,CXCR4 的使用频率很高。
High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore.
机构信息
Institute of Infectious Disease and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore 308433, Singapore.
出版信息
BMC Infect Dis. 2013 Feb 19;13:90. doi: 10.1186/1471-2334-13-90.
BACKGROUND
Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naïve HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection.
METHODS
V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naïve patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR) cut-offs, 10% and 5.75% were selected for tropism testing.
RESULTS
Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100%) CRF51_01B-infected subjects and 26 (40.6%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9%) subtype B subjects and 1 (11.1%) CRF33_01B-infected subject (P < 0.001). At FPR=5.75%, 10 (100%) CRF51_01B-infected subjects and 20 (31.3%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 4 (14.8%) subtype B and 1 (11.1%) CRF33_01B-infected subjects (P < 0.001). Among those with evidence of seroconversion within 2 years prior to study enrolment, 100% of CRF51_01B-infected subjects had CXCR4-using virus, independent of Geno2pheno FPR.
CONCLUSION
CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.
背景
最近的研究表明,HIV-1 亚型之间存在共受体使用的差异。我们研究了新加坡未经治疗的 HIV-1 患者中 HIV-1 亚型与共受体使用之间的相关性。此外,我们还研究了感染阶段是否会影响亚型共受体的相关性。
方法
从 110 名未经治疗的 HIV 患者中获得 HIV-1 包膜蛋白 gp120 的 V3 序列,并使用 Geno2pheno 进行基因型共受体嗜性测定。选择了两个假阳性率(FPR)截断值,即 10%和 5.75%,用于嗜性检测。
结果
基于 HIV-1 pol、gp120 和 gp41 的部分测序,对 110 名 HIV 感染者的病毒株进行了亚型分配:27 株为亚型 B,64 株为 CRF01_AE,10 株为 CRF51_01B,9 株为其他亚型。在 FPR=10%时,10(100%)株 CRF51_01B 感染的患者和 26(40.6%)株 CRF01_AE 感染的患者有 CXCR4 使用的病毒,而 7(25.9%)株亚型 B 患者和 1(11.1%)株 CRF33_01B 感染的患者没有(P < 0.001)。在 FPR=5.75%时,10(100%)株 CRF51_01B 感染的患者和 20(31.3%)株 CRF01_AE 感染的患者有 CXCR4 使用的病毒,而 4(14.8%)株亚型 B 患者和 1(11.1%)株 CRF33_01B 感染的患者没有(P < 0.001)。在研究入组前 2 年内有血清转换证据的患者中,100%的 CRF51_01B 感染患者有 CXCR4 使用的病毒,与 Geno2pheno 的 FPR 无关。
结论
与感染亚型 B 的患者相比,CRF51_01B 和 CRF01_AE 感染的患者更有可能使用 CXCR4。进一步研究这些差异可以帮助优化这些亚型人群中使用 CCR5 拮抗剂,并增加我们对 HIV-1 生物学的理解。
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