Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de virologie, Paris, France.
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), AP-HP, Hôpital Saint Antoine, Laboratoire de virologie, Paris, France.
J Antimicrob Chemother. 2021 Jul 15;76(8):2148-2152. doi: 10.1093/jac/dkab123.
APOBEC3 editing activity contributes to sequences variation and viral diversification. We aimed to characterize virological and clinical factors associated with G-to-A mutations and stop codons in the HIV-1 reservoir, markers of APOBEC3 footprints, in order to better understand HIV-1 diversity among virologically suppressed HIV-1-infected patients.
Immuno-virological and clinical factors were compared between 92 patients harbouring G-to-A mutations and stop codons (APOBEC+) in the reverse transcriptase gene and 92 patients without G-to-A mutations (APOBEC-) and stop codons in their DNA genotypes.
Patients were predominantly men (74.5%) and were mostly infected by B-subtype (69.0%), with 44.1% and 55.9% in APOBEC+ and APOBEC- groups, respectively. At time of HIV DNA genotypes, the total cell-associated HIV-1 DNA load was 2.34 log10 copies/106 cells (IQR 1.85-2.67) and 33.2% of them had a detectable ultrasensitive plasma viral load. Hypermutated sequences were identified in 28.2% of the APOBEC+ group. The median total cell-associated HIV-1 DNA level was significantly lower in APOBEC+ than APOBEC- group: 2.13 log10 copies/106 cells (IQR 1.60-2.60) versus 2.52 log10 copies/106 cells (IQR 2.19-2.71) (P < 0.001), respectively. Presence of G-to-A mutations and stop codon was independently associated with HIV-1 subtype non-B (P = 0.017).
These results show an independent association between the presence of G-to-A mutations and stop codons with HIV-1 subtype non-B and low proviral DNA that could be explained by the APOBEC3 footprints and restriction of DNA synthesis and integration. However, further investigations are needed to study the contribution of Vif amino acid variability among HIV-1 subtypes.
APOBEC3 编辑活性导致序列变异和病毒多样化。我们旨在描述与 HIV-1 储库中 G 到 A 突变和终止密码子相关的病毒学和临床因素，这些因素是 APOBEC3 足迹的标志物，以便更好地了解病毒学抑制的 HIV-1 感染患者中 HIV-1 的多样性。
比较了 92 名 HIV-1 逆转录酶基因中存在 G 到 A 突变和终止密码子（APOBEC+）的患者与 92 名 DNA 基因型中无 G 到 A 突变和终止密码子的患者（APOBEC-）的免疫病毒学和临床因素。
患者主要为男性（74.5%），主要感染 B 亚型（69.0%），APOBEC+和 APOBEC-组分别为 44.1%和 55.9%。在 HIV DNA 基因型时，细胞相关 HIV-1 DNA 总负荷为 2.34 log10 拷贝/106 细胞（IQR 1.85-2.67），其中 33.2%的患者可检测到超敏血浆病毒载量。APOBEC+组中有 28.2%的序列发生高度突变。APOBEC+组的细胞相关 HIV-1 DNA 总水平明显低于 APOBEC-组：2.13 log10 拷贝/106 细胞（IQR 1.60-2.60）与 2.52 log10 拷贝/106 细胞（IQR 2.19-2.71）（P<0.001）。存在 G 到 A 突变和终止密码子与 HIV-1 非 B 亚型独立相关（P=0.017）。
这些结果表明，G 到 A 突变和终止密码子的存在与 HIV-1 非 B 亚型和低前病毒 DNA 之间存在独立关联，这可能是由于 APOBEC3 足迹以及 DNA 合成和整合的限制所致。然而，需要进一步研究来研究 HIV-1 亚型中 Vif 氨基酸变异性的贡献。
