Samira Joussef-Piña, Immaculate Nankya, Sophie Nalukwago, Joy Baseke, Sandra Rwambuya, Dane Winner, Fred Kyeyune, Keith Chervenak, Bonnie Thiel, Robert Asaad, Curtis Dobrowolski, Benjamin Luttge, Blair Lawley, Cissy M Kityo, W Henry Boom, Jonathan Karn, Miguel E Quiñones-Mateu
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The peripheral HIV-1 reservoir, i.e., cell-associated HIV-1 RNA and proviral DNA, was characterized using our novel deep sequencing-based EDITS assay. Ugandan patients were slightly younger (median age 43 vs 49 years) and had slightly lower CD4<sup>+</sup> counts (508 vs 772 cells/ml) than U.S. individuals. All Ugandan patients were infected with non-B HIV-1 subtypes (31% A1, 64% D, or 5% C), while all U.S. individuals were infected with subtype B viruses. Unexpectedly, we observed a significantly larger peripheral inducible HIV-1 reservoir in U.S. patients compared to Ugandan individuals (48 vs. 11 cell equivalents/million cells, p < 0.0001). This divergence in reservoir size was verified measuring proviral DNA (206 vs. 88 cell equivalents/million cells, p < 0.0001). 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引用次数: 0
摘要
背景：我们对外周人类免疫缺陷病毒 1 型（HIV-1）库的了解主要偏向于 B 亚型 HIV-1 株系，从感染非 B 亚型 HIV-1 株系的患者那里获得的信息非常有限，而非 B 亚型 HIV-1 株系是非洲和亚洲中低收入国家（LMIC）的主要病毒：在这项研究中，从乌干达（n = 62）或美国（n = 50）监测到的接受过良好抑制性抗逆转录病毒疗法（ART）治疗的 HIV-1 患者中采集了血液样本，这些患者的血浆 HIV-1 载量 + T 细胞计数 > 300 cells/ml。利用我们基于深度测序的新型 EDITS 检测方法，对外周 HIV-1 储库（即细胞相关 HIV-1 RNA 和前病毒 DNA）进行了鉴定。与美国患者相比，乌干达患者略显年轻（中位年龄为 43 岁对 49 岁），CD4+ 细胞数（508 个细胞对 772 个细胞/毫升）略低。所有乌干达患者都感染了非 B 型 HIV-1 亚型（31% A1、64% D 或 5% C），而所有美国患者都感染了 B 亚型病毒。意想不到的是，与乌干达人相比，我们观察到美国患者的外周诱导型 HIV-1 储库明显更大（48 对 11 个细胞当量/百万细胞，P 结论）：乌干达患者的外周 HIV-1 储库较小，但更多样化，这可能与病毒（如细胞病理学较高的非 B 亚型）和/或宿主（如合并感染或合并疾病的发生率较高，导致克隆扩增较少）因素有关。这凸显了了解不同人群中病毒库动态的必要性，这也是目前在低收入和中等收入国家寻找HIV-1感染功能性治愈方法的努力的一部分。
Reduced and highly diverse peripheral HIV-1 reservoir in virally suppressed patients infected with non-B HIV-1 strains in Uganda.
Background: Our understanding of the peripheral human immunodeficiency virus type 1 (HIV-1) reservoir is strongly biased towards subtype B HIV-1 strains, with only limited information available from patients infected with non-B HIV-1 subtypes, which are the predominant viruses seen in low- and middle-income countries (LMIC) in Africa and Asia.
Results: In this study, blood samples were obtained from well-suppressed ART-experienced HIV-1 patients monitored in Uganda (n = 62) or the U.S. (n = 50), with plasma HIV-1 loads < 50 copies/ml and CD4+ T-cell counts > 300 cells/ml. The peripheral HIV-1 reservoir, i.e., cell-associated HIV-1 RNA and proviral DNA, was characterized using our novel deep sequencing-based EDITS assay. Ugandan patients were slightly younger (median age 43 vs 49 years) and had slightly lower CD4+ counts (508 vs 772 cells/ml) than U.S. individuals. All Ugandan patients were infected with non-B HIV-1 subtypes (31% A1, 64% D, or 5% C), while all U.S. individuals were infected with subtype B viruses. Unexpectedly, we observed a significantly larger peripheral inducible HIV-1 reservoir in U.S. patients compared to Ugandan individuals (48 vs. 11 cell equivalents/million cells, p < 0.0001). This divergence in reservoir size was verified measuring proviral DNA (206 vs. 88 cell equivalents/million cells, p < 0.0001). However, the peripheral HIV-1 reservoir was more diverse in Ugandan than in U.S. individuals (8.6 vs. 4.7 p-distance, p < 0.0001).
Conclusions: The smaller, but more diverse, peripheral HIV-1 reservoir in Ugandan patients might be associated with viral (e.g., non-B subtype with higher cytopathicity) and/or host (e.g., higher incidence of co-infections or co-morbidities leading to less clonal expansion) factors. This highlights the need to understand reservoir dynamics in diverse populations as part of ongoing efforts to find a functional cure for HIV-1 infection in LMICs.
期刊介绍：
Retrovirology is an open access, online journal that publishes stringently peer-reviewed, high-impact articles on host-pathogen interactions, fundamental mechanisms of replication, immune defenses, animal models, and clinical science relating to retroviruses. Retroviruses are pleiotropically found in animals. Well-described examples include avian, murine and primate retroviruses.
Two human retroviruses are especially important pathogens. These are the human immunodeficiency virus, HIV, and the human T-cell leukemia virus, HTLV. HIV causes AIDS while HTLV-1 is the etiological agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology aims to cover comprehensively all aspects of human and animal retrovirus research.
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