Perspective - (2025) Volume 9, Issue 4
Received: 01-Jul-2025, Manuscript No. vcrh-26-180157;
Editor assigned: 03-Jul-2025, Pre QC No. P-180157;
Reviewed: 17-Jul-2025, QC No. Q-180157;
Revised: 22-Jul-2025, Manuscript No. R-180157;
Published:
29-Jul-2025
, DOI: 10.37421/2736-657X.2025.9.316
Citation: Santos, Miguel. ”Viral Persistence: Diverse Evasion, Latency and Chronic Strategies.” Virol Curr Res 09 (2025):316.
Copyright: © 2025 Santos M. 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.
Viral persistence, a complex phenomenon, is often dictated by the intricate strategies viruses employ to subvert host defenses and establish long-term infections. These mechanisms are diverse, ranging from the direct manipulation of immune cell function to the establishment of dormant viral states [1].
Understanding these viral tactics is paramount for developing effective treatments against chronic viral diseases. The human immunodeficiency virus (HIV) exemplifies this challenge through its ability to establish latent reservoirs within resting CD4+ T cells. These reservoirs are transcriptionally silent, rendering them invisible to the immune system and antiretroviral therapies, which presents a substantial hurdle to complete viral eradication [2].
Consequently, a significant focus of current research is dedicated to identifying and targeting these latent viral reservoirs. Hepatitis B virus (HBV) infection can lead to chronic disease primarily due to the persistence of its covalently closed circular DNA (cccDNA) intermediate. This cccDNA serves as a stable, episomal template for viral replication, enduring within hepatocytes and demonstrating remarkable resistance to host immune responses and antiviral interventions, thereby contributing to long-term viral persistence and the ensuing pathogenesis [3].
Herpes simplex virus (HSV) is adept at establishing lifelong latent infections, predominantly residing within sensory neurons. During these latent phases, viral gene expression is significantly attenuated, enabling the virus to circumvent immune surveillance mechanisms. Reactivation is often triggered by stressors, leading to recurrent episodes of disease, underscoring a complex interplay between viral determinants and the host cellular milieu [4].
Cytomegalovirus (CMV) establishes persistent infections that can endure throughout an individual's lifetime, affecting a substantial portion of the human population. Viral persistence is maintained through a delicate equilibrium with the host immune system, wherein CMV possesses the capacity to modulate immune cell functions and evade detection, particularly in individuals with compromised immune systems, thereby leading to significant morbidity [5].
The Epstein-Barr virus (EBV) establishes lifelong latent infections, with a predilection for B lymphocytes. It deploys a variety of latency programs that not only facilitate viral persistence but also promote host cell survival and proliferation, often resulting in asymptomatic carriage. However, these processes are also implicated in lymphoproliferative disorders and certain forms of cancer. Comprehending these intricate latency programs is fundamental to developing strategies for targeting chronic EBV infections [6].
Persistent infections with papillomaviruses (PVs), especially those of high-risk oncogenic types, are demonstrably linked to the development of various cancers. PVs achieve persistence by integrating their genetic material into the host cell's DNA, which consequently leads to the dysregulation of crucial viral oncogenes such as E6 and E7. These viral oncoproteins actively interfere with the host cell's intrinsic mechanisms governing cell cycle control and apoptosis, thereby promoting uncontrolled cellular proliferation and the subsequent development of tumors [7].
Viral evasion of the host immune system represents a fundamental aspect underlying the establishment and maintenance of chronic infections. Viruses have evolved a diverse array of strategies to achieve this, including the disruption of antigen presentation pathways, the modulation of cytokine signaling cascades, and the induction of immune tolerance. These sophisticated mechanisms enable the virus to persist and replicate, often throughout the entire lifespan of the host, ultimately leading to the manifestation of chronic disease [8].
Chronic lymphocytic choriomeningitis virus (LCMV) infection in murine models offers a valuable experimental platform for dissecting the mechanisms of viral persistence. Key factors contributing to persistence include the induction of immune tolerance, incomplete viral clearance, and the establishment of a viral reservoir capable of evading adaptive immune responses. This model system is indispensable for advancing our understanding of the complex host-pathogen dynamics inherent in chronic viral infections [9].
Noroviruses, while primarily recognized as a leading cause of acute gastroenteritis, can also establish persistent infections under specific circumstances, particularly in immunocompromised individuals. Such chronic infections are associated with prolonged periods of viral shedding and have been implicated in the pathogenesis of inflammatory bowel disease. Elucidating the underlying factors that drive persistent norovirus infections is thus crucial for effective management of this significant public health challenge [10].
Viral persistence is a multifaceted challenge in virology, often dependent on the virus's ability to circumvent host immune responses, enter latent states, or establish chronic replication. These survival strategies can involve direct interference with immune cell functions, integration into the host genome, or the development of resistance to antiviral treatments. A comprehensive understanding of these viral mechanisms is essential for the development of effective therapeutic interventions targeting chronic viral infections [1].
The human immunodeficiency virus (HIV) masterfully employs sophisticated strategies to ensure its lifelong persistence within the host. A primary mechanism involves the establishment of latent reservoirs, primarily within resting CD4+ T cells. These reservoirs are characterized by transcriptional silence, rendering them effectively invisible to both the host's immune system and existing antiretroviral drugs. This characteristic poses a significant obstacle to achieving complete viral eradication, driving current research efforts towards identifying and targeting these elusive latent reservoirs [2].
Hepatitis B virus (HBV) infection can progress to a chronic state largely due to the presence and persistence of its covalently closed circular DNA (cccDNA) intermediate. This cccDNA functions as a remarkably stable, episomal template for continuous viral replication. It persists within hepatocytes and exhibits significant resistance to the host's immune defenses and available antiviral therapies, thereby playing a crucial role in long-term viral persistence and the progression of liver disease [3].
Herpes simplex virus (HSV) is well-known for its ability to establish lifelong latent infections, typically establishing residence in sensory neurons. During the latent phase, viral gene expression is dramatically reduced, allowing the virus to effectively evade immune surveillance. Reactivation of the virus, often triggered by stressful conditions, leads to recurrent episodes of clinical disease, highlighting a complex and dynamic interplay between viral factors and the host cellular environment [4].
Cytomegalovirus (CMV) establishes persistent infections that can last a lifetime in a substantial proportion of the human population. The maintenance of viral persistence is achieved through a delicate balance with the host immune system. CMV can modulate the function of immune cells and evade immune detection, particularly in individuals with compromised immunity, which can lead to severe illness and morbidity [5].
The Epstein-Barr virus (EBV) establishes lifelong latent infections, with its primary sanctuary being B lymphocytes. EBV utilizes a variety of distinct latency programs that enable its persistence while simultaneously promoting the survival and proliferation of host cells. Although this often leads to asymptomatic carriage, EBV is also associated with lymphoproliferative disorders and certain types of cancer. Understanding these intricate latency programs is paramount for developing targeted therapies against chronic EBV infection [6].
Persistent infections with papillomaviruses (PVs), particularly those classified as high-risk types, are strongly associated with the development of cancer. PVs achieve long-term persistence by integrating their genetic material into the host cell's DNA. This integration event leads to the aberrant expression and dysregulation of viral oncogenes, such as E6 and E7. These viral oncoproteins interfere with critical host cellular processes, including cell cycle control and apoptosis, thereby fostering uncontrolled cell proliferation and ultimately contributing to tumorigenesis [7].
Viral evasion of the host immune system is a fundamental prerequisite for the establishment and maintenance of chronic infections. Viruses employ a diverse repertoire of strategies to achieve immune evasion, including interfering with antigen presentation pathways, modulating cytokine signaling, and inducing immune tolerance. These sophisticated mechanisms allow viruses to persist and replicate within the host, often for extended periods, sometimes for the entire lifespan, leading to chronic disease states [8].
Chronic lymphocytic choriomeningitis virus (LCMV) infection in mice serves as a valuable and well-established model for investigating the complex mechanisms underlying viral persistence. The key factors contributing to chronic infection in this model include the induction of immune tolerance, incomplete viral clearance by the host, and the establishment of a persistent viral reservoir that can effectively evade adaptive immune responses. This model is instrumental in elucidating the intricate host-pathogen dynamics characteristic of chronic viral infections [9].
Noroviruses, a major cause of acute gastroenteritis worldwide, can also establish persistent infections in specific populations, notably in immunocompromised individuals. These chronic infections are characterized by prolonged viral shedding and can contribute to the development or exacerbation of inflammatory bowel disease. Therefore, a thorough understanding of the factors that drive persistent norovirus infection is critical for the effective management of this significant public health concern [10].
Viral persistence relies on mechanisms that allow viruses to evade host immunity, enter latent states, or establish chronic replication. Examples include HIV's latent reservoirs in CD4+ T cells, HBV's persistent cccDNA, HSV's latency in neurons, CMV's immune modulation, EBV's latency programs in B cells, and PVs integrating into host DNA to promote cancer. Viruses use diverse strategies like interfering with antigen presentation and cytokine signaling to evade immune detection. Chronic LCMV infection in mice models these dynamics, while noroviruses can cause persistent infections in immunocompromised individuals. Understanding these persistence strategies is crucial for developing effective treatments against chronic viral diseases.
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