Brief Report - (2025) Volume 9, Issue 6
Received: 01-Nov-2025, Manuscript No. vcrh-26-180182;
Editor assigned: 03-Nov-2025, Pre QC No. P-180182;
Reviewed: 17-Nov-2025, QC No. Q-180182;
Revised: 24-Nov-2025, Manuscript No. R-180182;
Published:
29-Nov-2025
, DOI: 10.37421/2736-657X.2025.9.333
Citation: Nguyen, Thomas. ”Autophagy’s Dual Role in Viral Infections: A New Antiviral Target.” Virol Curr Res 09 (2025):333.
Copyright: © 2025 Nguyen T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Autophagy, a fundamental cellular process involved in the degradation and recycling of damaged organelles and misfolded proteins, exhibits a complex and often contradictory role in viral infections. This cellular housekeeping mechanism can serve as a double-edged sword, functioning as both a defense strategy to eliminate invading viruses and a facilitator of viral replication by providing essential resources [1].
Viruses have evolved sophisticated strategies to manipulate this cellular pathway, frequently hijacking autophagic machinery for their own propagation and survival [2].
Understanding these intricate interactions is paramount for the development of effective antiviral therapies [1].
Conversely, autophagy also acts as a potent intrinsic defense mechanism, actively degrading viral particles, eliminating infected host cells, and clearing compromised organelles. The cell's innate immune response often involves the activation of autophagic pathways to sequester and neutralize viral invaders. Therefore, strategies aimed at enhancing or activating autophagy hold significant promise as therapeutic avenues for combating a wide spectrum of viral infections [3].
The intricate balance of autophagy's involvement in viral pathogenesis is heavily influenced by the specific viral species and the cellular context in which the infection occurs [4].
Different viral families and even distinct strains within a single family can exhibit varied interactions with autophagy pathways, either promoting or inhibiting them. This nuanced regulation underscores the critical need for the development of virus-specific therapeutic interventions that can precisely target these complex host-pathogen interactions [4].
The field is rapidly advancing, with significant research focused on developing novel drugs that can modulate autophagy for antiviral purposes [5].
Some viruses, such as Dengue virus and Hepatitis C virus (HCV), have been demonstrably shown to induce the formation of autophagosomes, a process that is indispensable for their replication cycle. These viruses exploit the autophagosome membrane as a crucial platform for viral RNA replication and the subsequent assembly of new viral progeny, clearly illustrating their direct reliance on this cellular process [6].
In stark contrast, other viruses, including certain strains of influenza virus, are effectively degraded by the autophagic machinery. This clearance mechanism is a critical component of the host's defense repertoire, often involving the formation of autophagosomes that subsequently fuse with lysosomes, leading to the destruction of viral components and effectively limiting the spread of the infection [7].
The autophagy-related genes (ATGs) are universally recognized as the core components responsible for orchestrating the entire autophagic process. A detailed understanding of how specific viral proteins interact with these ATG proteins offers invaluable insights into the molecular mechanisms by which viruses either subvert or strategically utilize the host's autophagy pathways. This knowledge can pave the way for the identification of novel targets for the development of antiviral drugs [8].
The role of autophagy in the context of chronic viral infections, such as those caused by HIV and HBV, represents a significant and ongoing area of scientific inquiry. Autophagy can contribute to viral persistence by mechanisms such as limiting inflammatory responses or by facilitating the maintenance of viral reservoirs. However, it can also play a beneficial role by aiding in the clearance of infected cells. This highlights the context-dependent nature of autophagy's involvement in chronic viral diseases, making it a critical factor to consider in therapeutic strategies [9].
A crucial aspect of deciphering autophagy's role in viral infections involves investigating the precise stage of the viral life cycle that is influenced by this cellular process. Viruses may rely on autophagy for entry into the host cell, for their intracellular replication or assembly, or even for their egress from the infected cell. Comprehending these specific dependencies is essential for designing targeted antiviral strategies that effectively disrupt these critical interactions between the virus and the host cell's autophagic machinery [10].
The therapeutic potential of targeting autophagy for antiviral purposes is a rapidly expanding frontier. Compounds designed to selectively induce the autophagic clearance of viruses, or conversely, to inhibit the ways in which viruses manipulate autophagy, are showing considerable promise for the development of novel antiviral therapies. This research encompasses the exploration of both small molecule interventions and broader host-directed therapeutic strategies [5].
The complexity of autophagy's dual role necessitates a detailed understanding of the specific molecular players involved. For instance, certain viral proteins have been identified that can directly interact with and modulate the activity of key autophagy-related proteins, thereby tipping the balance towards either viral replication or clearance [8].
This intricate molecular crosstalk is a prime example of the adaptive strategies viruses employ to exploit host cell machinery for their own benefit [2].
Ultimately, the profound impact of autophagy on viral infections, ranging from its function as a defense mechanism to its exploitation by viruses, underscores its central importance in virology. The ongoing research into this dynamic interplay promises to yield innovative approaches to combatting infectious diseases through precisely targeted interventions [1, 3, 4, 5, 8, 10].
Autophagy plays a dual role in viral infections, acting as both a defense mechanism to eliminate viruses and a pro-viral factor by providing essential resources for replication. This cellular process, responsible for degrading damaged organelles and misfolded proteins, can be hijacked by viruses to promote their survival and spread. Understanding this complex interplay is crucial for developing novel antiviral strategies [1].
Viruses have evolved sophisticated mechanisms to manipulate autophagy, often inducing it to create autophagosomes that serve as replication sites. Some viruses also interfere with the lysosomal degradation step, preventing the clearance of viral components. This highlights the adaptive strategies viruses employ to exploit host cell machinery [2].
Conversely, autophagy can act as a potent antiviral mechanism by degrading viral particles, infected cells, and damaged organelles. The cell initiates autophagic pathways to sequester and eliminate viral invaders. Activating or enhancing autophagy could therefore represent a therapeutic avenue for combating viral infections [3].
The balance between pro-viral and antiviral roles of autophagy is often determined by the specific virus and the host cell context. Different viral families and even strains within a family can differentially engage or antagonize autophagy pathways. This intricate regulation underscores the need for virus-specific therapeutic interventions [4].
Research into autophagy-modulating drugs is gaining momentum. Compounds that can selectively induce autophagic clearance of viruses, or inhibit viral manipulation of autophagy, hold promise for novel antiviral therapies. This includes exploring both small molecules and host-directed strategies [5].
Specific viruses, like Dengue virus and Hepatitis C virus, have been shown to induce autophagosome formation, which is essential for their replication. These viruses utilize the autophagosome membrane as a platform for viral RNA replication and assembly, demonstrating a direct dependence on this cellular process [6].
In contrast, other viruses, such as some strains of influenza virus, can be degraded by autophagy, indicating an effective host defense. This clearance can involve the formation of autophagosomes that fuse with lysosomes, leading to the destruction of viral components and limiting infection spread [7].
The autophagy-related genes (ATGs) are central to the autophagic process. Understanding how viral proteins interact with specific ATG proteins provides insights into the molecular mechanisms by which viruses subvert or utilize autophagy. This offers potential targets for antiviral drug development [8].
The role of autophagy in chronic viral infections, such as HIV and HBV, is also a significant area of research. Autophagy can contribute to viral persistence by limiting inflammation or promoting viral reservoirs, but it can also aid in clearing infected cells. The context-dependent nature of autophagy's involvement is a critical consideration [9].
Investigating the precise stage of the viral life cycle affected by autophagy is key. Some viruses rely on autophagy for entry, others for replication or assembly, and some for egress. Understanding these specific dependencies allows for the design of targeted antiviral strategies that disrupt these critical interactions [10].
The dual nature of autophagy in viral infections means that manipulating this pathway for therapeutic benefit requires careful consideration of the specific virus and host cell. For instance, while inducing autophagy might be beneficial against some viruses, it could potentially aid others if they exploit the process for replication [1, 2, 3, 4]. Therefore, therapies must be tailored to exploit the antiviral functions of autophagy or to block viral subversion of the process [5].
The molecular machinery of autophagy, primarily governed by the ATG proteins, is a focal point for understanding viral manipulation. Viral proteins can directly interact with these ATG proteins, altering their function to favor viral replication or survival [8].
Identifying these specific protein-protein interactions is crucial for designing highly targeted antiviral interventions [8].
Chronic viral infections present unique challenges where autophagy's role can be particularly complex. It might contribute to long-term viral persistence by modulating the immune response or protecting viral reservoirs, while simultaneously having the potential to eliminate infected cells [9].
This complex interplay necessitates nuanced therapeutic approaches that consider the long-term implications of autophagy modulation [9].
Understanding the specific stages of the viral life cycle influenced by autophagy is critical for effective intervention. Whether a virus uses autophagy for entry, replication, assembly, or egress, targeting these specific interactions can disrupt the entire infectious process [10].
This level of detail allows for the design of highly specific and potent antiviral agents [10].
In conclusion, the intricate relationship between autophagy and viral infections offers a rich landscape for therapeutic development. By dissecting the mechanisms of viral exploitation and harnessing the antiviral potential of autophagy, researchers are poised to develop novel and effective strategies to combat a wide range of viral diseases [1, 3, 5, 8, 10].
Autophagy plays a dual role in viral infections, acting as both a defense mechanism and a pro-viral factor. Viruses often hijack autophagy for replication and survival, while the cell also utilizes it to degrade viral particles. The specific interaction depends on the virus and host cell context. Research is focused on developing autophagy-modulating drugs for antiviral therapy, targeting specific stages of the viral life cycle or viral protein interactions with autophagy machinery. This complex interplay offers promising avenues for novel antiviral interventions, particularly for chronic viral infections.
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Virology: Current Research received 187 citations as per Google Scholar report
