Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.
Viruses. 2020 Dec 7;12(12):1404. doi: 10.3390/v12121404.
HIV-1 compartmentalization in reservoir sites remains a barrier to complete HIV eradication. It is unclear whether there is variation in HIV-1 and between cerebrospinal fluid (CSF) and plasma of individuals with HIV-associated cryptococcal meningitis (CM). We compared HIV-1 characteristics and the cytotoxic T-lymphocyte (CTL) escape mutations from CSF and plasma samples. Employing population-based Sanger sequencing, we sequenced HIV-1 from CSF of 25 patients and plasma of 26 patients. For , 15 CSF and 21 plasma samples were successfully sequenced. Of these, 18 and 9 were paired and CSF/plasma samples, respectively. There was no statistically significant difference in the proportion of CCR5-using strains in the CSF and plasma, ( = 0.50). Discordant CSF/plasma virus co-receptor use was found in 2/18 pairs (11.1%). The polymorphisms in the HIV-1 V3 loop were concordant between the two compartments. From the HIV-1 sequences, three pairs had discordant CTL escape mutations in three different epitopes of the nine analyzed. These findings suggest little variation in the HIV-1 between plasma and CSF and that the CCR5-using strains predominate in both compartments. HIV-1 CTL escape mutations also displayed little variation in CSF and plasma suggesting similar CTL selective pressure.
HIV-1 在储库部位的分隔仍然是完全清除 HIV 的障碍。目前尚不清楚 HIV 相关隐球菌性脑膜炎(CM)患者的脑脊液(CSF)和血浆中 HIV-1 和 的情况是否存在差异。我们比较了 HIV-1 的特征和细胞毒性 T 淋巴细胞(CTL)逃逸突变从 CSF 和血浆样本。采用基于人群的 Sanger 测序,我们对 25 例患者的 CSF 和 26 例患者的血浆中的 HIV-1 进行了测序。对于 ,成功测序了 15 例 CSF 和 21 例血浆样本。其中,18 对和 9 对 CSF/血浆样本分别配对。CSF 和血浆中 CCR5 使用株的比例没有统计学差异(=0.50)。在 18 对 CSF/血浆样本中发现了 2 对(11.1%)病毒共受体使用不匹配。两个隔室中 HIV-1 V3 环的多态性是一致的。从 HIV-1 序列中,在分析的 9 个表位中的 3 个不同表位中,有 3 对出现了 CTL 逃逸突变不匹配。这些发现表明,血浆和 CSF 之间的 HIV-1 差异很小,而且 CCR5 使用株在两个隔室中均占优势。CSF 和血浆中的 HIV-1 CTL 逃逸突变也很少有差异,表明相似的 CTL 选择压力。