Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA.
QuidelOrtho, Rochester, NY 14626, USA.
Viruses. 2023 Sep 20;15(9):1961. doi: 10.3390/v15091961.
SERINC5 is a restriction factor that becomes incorporated into nascent retroviral particles, impairing their ability to infect target cells. In turn, retroviruses have evolved countermeasures against SERINC5. For instance, the primate lentiviruses (HIV and SIV) use Nef, Moloney Murine Leukemia Virus (MLV) uses GlycoGag, and Equine Infectious Anemia Virus (EIAV) uses S2 to remove SERINC5 from the plasma membrane, preventing its incorporation into progeny virions. Recent studies have shown that SERINC5 also restricts other viruses, such as Hepatitis B Virus (HBV) and Classical Swine Fever Virus (CSFV), although through a different mechanism, suggesting that SERINC5 can interfere with multiple stages of the virus life cycle. To investigate whether SERINC5 can also impact other steps of the replication cycle of HIV, the effects of SERINC5 on viral transcripts, proteins, and virus progeny size were studied. Here, we report that SERINC5 causes significant defects in HIV gene expression, which impacts virion production. While the underlying mechanism is still unknown, we found that the restriction occurs at the transcriptional level and similarly affects plasmid and non-integrated proviral DNA (ectopic or non-self-DNA). However, SERINC5 causes no defects in the expression of viral RNA, host genes, or proviral DNA that is integrated in the cellular genome. Hence, our findings reveal that SERINC5's actions in host defense extend beyond blocking virus entry.
SERINC5 是一种限制因子，会整合到新生的逆转录病毒粒子中，从而损害它们感染靶细胞的能力。反过来，逆转录病毒已经进化出了针对 SERINC5 的对策。例如，灵长类慢病毒（HIV 和 SIV）使用 Nef，莫洛尼鼠白血病病毒（MLV）使用 GlycoGag，而马传染性贫血病毒（EIAV）使用 S2 将 SERINC5 从质膜中去除，防止其整合到子代病毒粒子中。最近的研究表明，SERINC5 还限制了其他病毒，如乙型肝炎病毒（HBV）和猪瘟病毒（CSFV），尽管通过不同的机制，这表明 SERINC5 可以干扰病毒生命周期的多个阶段。为了研究 SERINC5 是否也能影响 HIV 复制周期的其他步骤，研究了 SERINC5 对病毒转录物、蛋白质和病毒子代大小的影响。在这里，我们报告 SERINC5 会导致 HIV 基因表达的显著缺陷，从而影响病毒粒子的产生。虽然其潜在机制尚不清楚，但我们发现这种限制发生在转录水平，并且同样影响质粒和非整合的前病毒 DNA（异位或非自身 DNA）。然而，SERINC5 不会导致整合到细胞基因组中的病毒 RNA、宿主基因或前病毒 DNA 的表达出现缺陷。因此，我们的研究结果表明，SERINC5 在宿主防御中的作用不仅限于阻止病毒进入。
