Page 89 - JCTR-11-1

Journal of Clinical and
Translational Research Reprogram lipid droplet against viral infection

that YY1 played an active role in this process. Notably, the antiviral function of LDs. Following Zika virus and
the PRRSV virions, nucleocapsid proteins, dsRNA, and herpes simplex virus type 1 infection, the host protein
replication and transcription complex were found not to epidermal growth factor receptor-driven LD synthesis has
colocalize with intracellular LDs, indicating that the virus been shown to activate the expression of type Ⅰ and type III
does not rely on LDs for the assembly of progeny virions. interferons, thereby exerting antiviral effects. 12
In addition, exogenously induced LD synthesis inhibited Moreover, researchers have reported that the LD
PRRSV replication, suggesting that increased LD synthesis surface protein, viperin, interacts with the non-structural
observed after viral infection is likely a host cell strategy protein 5A of the hepatitis C virus to inhibit viral genome
to resist viral infection. This highlights that there is an replication. Hundreds of functional proteins are located
13
interaction between PRRSV and LDs, encompassing both on the surface of mature LDs, and their potential roles
viral utilization and host resistance. Next, the researchers in virus-LD interactions remain to be further elucidated.
explored the mechanism by which YY1 reprogrammed Further exploration of the mechanisms underlying
LD synthesis. They identified two lipid metabolism increased LD synthesis after virus infection and the
proteins, fatty acid synthase (FASN) and peroxisome corresponding antiviral responses from the perspective of
proliferator-activated receptor gamma (PPARγ), whose the host is essential to understand the complex dynamics
gene expression was regulated by YY1 and reported that of virus-LD dynamic interactions fully.
YY1 exerts antiviral effects by negatively regulating the
FASN-mediated fatty acid synthesis pathway and positively Acknowledgments
regulating the PPARγ-mediated LD synthesis pathway.
None.
The study investigated a previously unexplored aspect
of virus-host interactions: host cell reprogramming of Funding
LD synthesis to resist viral infection. It provides new
insights into the interaction of PRRSV with LDs and, None.
for the 1 time, elucidates how host cells reprogram LD Conflict of interest
st
synthesis through YY1 in response to viral infection. This
novel insight not only expands our understanding of the None.
dynamic mechanism of LD synthesis but also complements
the existing theories of the antiviral activity of LDs. By Author contributions
elucidating the antiviral function of LD synthesis and This is a single-authored article.
the role of YY1 in this context, this study provides a
foundation for the development of treatment strategies Ethics approval and consent to participate
and innovative prevention strategies for viral infection. For Not applicable.
example, this study designed rigorous in vitro and in vivo
experiments on YY1 and identified the antiviral function Consent for publication
of YY1 and its potential therapeutic target through
comprehensive analysis. In addition, this study provides Not applicable.
a possible explanation for puzzling phenomena, such as Availability of data
the increase in LD synthesis after viral infection. Previous
studies have shown that PRRSV induces lipophagy and Not applicable.
releases fatty acids for viral replication. If the increase
11
in LDs results from active induction by PRRSV, the virus References
could directly hijack the fatty acids synthesized by LDs for 1. Cui Z, Liu J, Xie C, et al. High-throughput screening unveils
its replication, bypassing the need for inducing synthesis nitazoxanide as a potent PRRSV inhibitor by targeting
followed by lipolysis. Increasing LD synthesis may serve as NMRAL1. Nat Commun. 2024;15(1):4813.
a host defense mechanism against viral infection, but the doi: 10.1038/s41467-024-48807-y
virus may evolve countermeasures to induce LDs lipolysis
into fatty acids to supply energy for viral replication. 2. Gao P, Liu Y, Wang H, et al. Viral evasion of PKR restriction
by reprogramming cellular stress granules. Proc Natl Acad
This dynamic reflects the coexistence of resistance and Sci U S A. 2022;119(29):e2201169119.
utilization between LDs and viruses. At present, most
studies are interested in viruses hijacking and utilizing doi: 10.1073/pnas.2201169119
LDs and exploring the underlying mechanism from 3. Ke W, Zhou Y, Lai Y, Long S, Fang L, Xiao S. Porcine
different perspectives. However, few studies have clarified reproductive and respiratory syndrome virus nsp4 positively

Volume 11 Issue 1 (2025) 83 doi: 10.36922/jctr.24.00039