Scholarlink

Background <p>In the early phase of HIV infection, as studied in vitro, high levels of unintegrated (both linear and circular) and integrated (provirus) forms of viral DNA are seen, and cells produce high levels of virus. In time, the level of unintegrated DNA declines, followed by a progressive decline in virus expression. Extensive studies of the proviral landscape in people living with HIV (PLWH) on antiretroviral therapy (ART) show that only about 2% of proviruses are intact; the remainder are characterized as defective and contain numerous deletions of proviral DNA segments and hypermutations. In the current study, we investigated the decline of viral expression in infected T cells in search of mechanisms involved in proviral inactivation.</p> Results <p>We derived clonal lines from Jurkat cells infected with HIV MN and monitored them for viral expression over time in culture. In a subset of clones that displayed a decline in expression, we found provirus containing large deletions and the integration of a retrotranscribed molecule of tRNA<sup>Gly</sup> adjacent to the 3’-end of the proviral DNA. We provide evidence linking the proviral deletions to the insertion of a reverse transcribed tRNA<sup>Gly</sup> molecule and propose a mechanism for its self-primed reverse transcription.</p> Conclusions <p>Large deletions of proviral DNA have been reported in PLWH on ART and attributed to errors that occurred in the synthesis of the minus strand during the reverse transcription of the viral genome. Our results support an additional mechanism for proviral deletions, mediated by tRNA<sup>Gly</sup>, in the inactivation of the provirus.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

t-RNA mediates provirus deletion in HIV-infected cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

查看全文
  • Corrado Gurgo,
  • Genoveffa Franchini

摘要

Background

In the early phase of HIV infection, as studied in vitro, high levels of unintegrated (both linear and circular) and integrated (provirus) forms of viral DNA are seen, and cells produce high levels of virus. In time, the level of unintegrated DNA declines, followed by a progressive decline in virus expression. Extensive studies of the proviral landscape in people living with HIV (PLWH) on antiretroviral therapy (ART) show that only about 2% of proviruses are intact; the remainder are characterized as defective and contain numerous deletions of proviral DNA segments and hypermutations. In the current study, we investigated the decline of viral expression in infected T cells in search of mechanisms involved in proviral inactivation.

Results

We derived clonal lines from Jurkat cells infected with HIV MN and monitored them for viral expression over time in culture. In a subset of clones that displayed a decline in expression, we found provirus containing large deletions and the integration of a retrotranscribed molecule of tRNAGly adjacent to the 3’-end of the proviral DNA. We provide evidence linking the proviral deletions to the insertion of a reverse transcribed tRNAGly molecule and propose a mechanism for its self-primed reverse transcription.

Conclusions

Large deletions of proviral DNA have been reported in PLWH on ART and attributed to errors that occurred in the synthesis of the minus strand during the reverse transcription of the viral genome. Our results support an additional mechanism for proviral deletions, mediated by tRNAGly, in the inactivation of the provirus.