需要ORF48才能实现卡波西肉瘤相关疹病毒的最优临床复制
Beatriz H S Veronese1,2, Amy Nguyen1, Khushil Patel1
1Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, USA.
bioRxiv : the preprint server for biology
|March 11, 2024
概括
卡波西卡波西 (Kaposi Kaposi) 是一个
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 卡波西的肉瘤相关性疹病毒 (KSHV) 通过病毒蛋白质逃避宿主免疫力.
- 这种cGAS-STING通路对于对KSHV重新激活的天生的免疫力至关重要.
- KSHV编码的蛋白质可以抑制cGAS-STING通路的病毒持久性.
研究的目的:
- 调查KSHV ORF48在调节cGAS-STING通路和KSHV光学复制中的作用.
- 阐明ORF48影响天生的免疫力和病毒生命周期的机制.
主要方法:
- 在KSHV模型中使用siRNA和ORF48删除系统.
- 进行了共同免疫沉以评估ORF48-STING相互作用.
- 在ORF48表达细胞和KSHV光学系统中分析了STING依赖的免疫信号.
- 评估病毒基因转录,蛋白质表达,基因组复制和病毒产生.
主要成果:
- ORF48对于最佳的KSHV光学复制是必不可少的,影响基因转录,蛋白质表达和病毒产生.
- ORF48与STING相互作用,并抑制STING依赖的先天免疫信号传递.
- 在KSHV溶解周期中ORF48的损失并没有取消IFNβ的产生,这表明有冗余的机制.
结论:
- 通过调节cGAS-STING通路,ORF48在促进KSHV的临床复制方面发挥着至关重要的作用.
- 虽然ORF48与STING相互作用,但其在KSHV光学复制过程中的功能可能涉及其他尚未发现的机制.
- 需要进一步的研究才能充分理解ORF48在KSHV病变发生过程中的多方面的作用.
相关概念视频
02:33Retroviruses
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
01:20Viral Replication: Lytic Cycle
Bacteriophages, or phages, are viruses that specifically infect bacteria. Among them, T-even bacteriophages, such as T4, exhibit a well-characterized lytic replication cycle in Escherichia coli (E. coli). This process ensures the rapid proliferation of the virus while ultimately leading to the destruction of the bacterial host.Attachment and DNA InjectionThe infection process begins with the recognition and binding of the T4 phage to the E. coli cell surface. Tail fibers of the phage...
01:28Herpes
Herpes simplex type 1 (HSV‑1) is a widespread pathogen responsible for orolabial lesions. It is an enveloped, double-stranded DNA (dsDNA) virus belonging to the family Herpesviridae. Once the virus infects a host cell, its double‑stranded DNA genome is delivered into the nucleus, where a coordinated cascade of immediate‑early, early, and late gene expression directs viral DNA replication, structural protein synthesis, and virion assembly. After primary infection of epithelial cells, HSV-1...
01:23Genital Herpes
Genital herpes is a sexually transmitted infection primarily caused by herpes simplex virus type 2 (HSV-2), though herpes simplex virus type 1 (HSV-1) is increasingly implicated in genital infections, particularly among younger populations. Transmission occurs mainly through sexual contact, with asymptomatic viral shedding serving as a major route of spread. This characteristic makes HSV-2 difficult to control at a population level, as individuals may unknowingly transmit the virus even in the...
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
01:22Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...