Herpes simplex virus (HSV), whether type 1 or type 2, is a master of persistence. Once it enters the body—often through a small break in the skin or mucous membrane—it travels along nerve pathways and settles into a kind of hibernation. This “latency” stage takes place deep within the nervous system, where the virus hides inside clusters of nerve cells known as ganglia. HSV-1 typically settles in the trigeminal ganglia near the face, while HSV-2 tends to lie dormant in the sacral ganglia near the base of the spine.
What makes herpes so tricky is that even though it can remain quiet for long stretches, it never fully goes away. Instead, it can reactivate—often during times of stress, illness, or immune suppression—causing new outbreaks of symptoms. This ability to come and go is one of the most frustrating aspects of living with herpes.
Despite this, the immune system plays a remarkable and ongoing role in keeping the virus in check. Specialized immune cells like CD8+ T cells are stationed in the nervous system’s ganglia, where they constantly monitor for signs of viral activity. When they detect the virus stirring, they act quickly—releasing signals like interferon-gamma to stop it from replicating. Even more impressively, a subset of these immune cells, called tissue-resident memory T cells, stay close to the original site of infection, providing a local line of defense that can respond almost instantly.
The body also relies on early, non-specific defenses—what’s known as the innate immune system. This includes everything from physical barriers like skin to frontline responders like interferons and supportive cells in the nervous system. These early defenses help slow the virus before the more specialized adaptive immune system can fully respond.
In this article, we’ll explore how herpes interacts with the immune system—not just during an active infection, but also during the long, silent periods when the virus lies low. By understanding how your body manages this ongoing relationship, you’ll gain insight into how herpes persists, how symptoms are controlled, and where researchers are focusing their efforts for future treatments and vaccines.
The First Line of Defense: Innate Immunity at Work
When herpes first enters the body—whether it’s the initial infection or a later reactivation—it doesn’t go unnoticed. The virus typically slips in through a break in the skin or a mucosal surface, infecting the outermost cells before making its way along the nerves to a permanent home in the body’s sensory ganglia. From there, it can lie dormant for years. But every so often, the virus can reactivate, traveling back down those same nerves to the skin or mucosa, where it may trigger a new outbreak.
Before the body’s more targeted defenses kick in, the innate immune system responds within hours. This early response doesn’t rely on prior exposure or immune memory—instead, it acts fast and broadly, working to contain the virus before it can spread further.
The skin and mucous membranes are the body’s first line of physical defense. These aren’t just passive barriers; they’re lined with cells like keratinocytes and Langerhans cells that can detect invaders like HSV. Once herpes is detected, these cells begin signaling for help by releasing chemical messengers—interferons and chemokines—that attract immune cells to the site of infection. Hidden in the lining of these tissues are also pattern recognition receptors, like Toll-like receptors, which sense the virus and activate downstream immune pathways to help fight it off.
Among the first responders are natural killer (NK) cells and macrophages. NK cells, primed by interferons, act swiftly to kill infected cells and release interferon-gamma, a powerful cytokine that helps stop the virus from replicating. Macrophages play a different but equally important role: they engulf infected cells and release pro-inflammatory signals like TNF-α and IL-12, which further activate NK cells and help coordinate the immune response.
Cytokines and interferons act as the body’s emergency broadcast system. Infected cells and specialized immune cells, such as plasmacytoid dendritic cells, produce type I interferons that spread through the surrounding tissue, setting up a state of antiviral readiness. These signals alert nearby cells, making them more resistant to infection and more efficient at presenting viral fragments to other immune cells.
Although the innate immune response doesn’t “remember” herpes, its role is vital. It buys time—slowing down the virus, limiting the spread, and creating the conditions needed for the adaptive immune system to take over. HSV, however, is not a passive opponent. It’s evolved ways to blunt this response, including tactics that suppress interferon production and help it escape early detection. Still, in most people, this initial line of defense plays a crucial role in containing the virus and keeping outbreaks shorter and less severe.
The Second Line of Defense: Adaptive Immunity
While the innate immune system buys the body time, it’s the adaptive immune system that provides long-term defense—and this is where things get highly specialized. Unlike the fast but generalized response of innate immunity, the adaptive response is targeted, memory-based, and crucial for managing herpes over the long haul.
At the center of this response are T cells, the immune system’s strategists and frontline fighters. CD8+ T cells, also known as cytotoxic T cells, are especially important in herpes control. These cells live right where the virus hides—in the sensory ganglia—and keep a constant watch for signs of reactivation. When HSV begins to stir, CD8+ T cells spring into action, releasing interferon-gamma to suppress viral replication. Some even form close, physical interactions with infected neurons, helping contain the virus without harming these vital cells.
Supporting them are CD4+ T cells, or helper T cells. Their job is to coordinate the immune response, ensuring that both antibody-producing B cells and memory-forming T cells stay active and effective. However, their involvement can be a double-edged sword: while they boost the immune system’s ability to fight HSV, they may also contribute to inflammation and tissue damage during severe or recurrent outbreaks.
B cells enter the scene with a different skill set—antibody production. These antibodies can neutralize free-floating virus particles, help reduce the spread of infection, and even protect against serious complications like herpes-related encephalitis. However, antibodies alone aren’t enough to clear the virus from its hiding spots. HSV is exceptionally good at lying low, and since antibodies can’t reach into the neurons where the virus hides, their role is more about controlling the virus during active stages than eliminating it altogether.
What makes the adaptive immune system especially powerful is its ability to remember. After encountering HSV, both CD4+ and CD8+ T cells form long-lived memory populations that can respond quickly to future reactivations. Some of these memory T cells, called tissue-resident memory (TRM) cells, stay in the same tissue where the virus first appeared—whether that’s the skin, genital area, or trigeminal region. This local presence gives the immune system a head start in responding to flare-ups.
Even with this intricate surveillance system, HSV remains a step ahead. During latency, the virus becomes almost invisible—producing very few proteins and expressing molecules that keep immune cells at bay. Neurons, the cells where HSV hides, are also less prone to immune destruction. This is intentional; the body can’t afford to lose its nerve cells in the fight against infection. As a result, the immune system walks a delicate line: it keeps the virus contained without causing damage to the nervous system itself.
That balance is why herpes is lifelong. Adaptive immunity can suppress the virus, reduce outbreaks, and protect against severe disease—but it cannot fully eliminate HSV. Still, this ongoing immune vigilance makes a significant difference in how the virus behaves, and it’s one reason why many people with HSV experience milder and less frequent outbreaks over time.
How the Body Controls Herpes Latency
Once herpes simplex virus (HSV) makes its way into the nervous system, it settles into a long-term state known as latency. In this phase, the virus tucks its genetic material into the nuclei of sensory neurons—often in the trigeminal ganglia near the face or sacral ganglia near the spine. It doesn’t replicate or produce new virus particles, but it’s not entirely dormant either. Even during latency, the immune system doesn’t stop paying attention.
This quiet stage is surprisingly active from an immunological perspective. Specialized immune cells, especially CD8+ T cells, are stationed in these ganglia and remain alert. These cells don’t just passively linger—they’re continually engaged with the neurons that harbor the virus. Through constant surveillance and antigen-driven activation, they help keep HSV suppressed, producing signals like interferon-gamma that prevent the virus from reawakening.
Occasionally, HSV begins to stir. It might start expressing early viral proteins—an initial step toward reactivation. But CD8+ T cells in the ganglia are ready. They detect these subtle changes and respond quickly, releasing antiviral molecules such as granzyme B and interferon-gamma to stop the virus in its tracks. Notably, they often do this without killing the neurons themselves. Instead of launching a full-on attack, these immune cells use non-destructive strategies to maintain the balance between controlling the virus and preserving the health of delicate nerve tissue.
However, this defense system has its limits. Neurons are considered “immune-privileged”—they’re naturally protected from aggressive immune activity because damage to them can have long-lasting consequences. HSV takes advantage of this. It minimizes its visibility by reducing viral protein expression and manipulating host signals that block immune cell infiltration. The virus even produces latency-associated transcripts (LATs), which help prevent neuron death and inhibit strong immune responses.
Because of these built-in protections, immune cells can’t easily enter neurons or fully eliminate HSV once it’s hidden away. Even though some CD8+ T cells remain active for years, others become exhausted over time, especially in the face of repeated or long-term infection. Still, a subset of highly functional T cells continues to patrol the ganglia, maintaining a kind of stalemate that favors immune control but stops short of viral eradication.
This ongoing tug-of-war explains why herpes is both persistent and manageable. The immune system doesn’t “lose”—it keeps the virus contained. But it also can’t fully win, because HSV has adapted so well to its neurological niche. Understanding this dynamic helps make sense of why outbreaks can still occur, even in people with strong immune systems, and why research continues to focus on strengthening this surveillance rather than eliminating the virus entirely.
What Weakens the Immune Response
The immune system is remarkably good at keeping herpes under control—but like any complex system, it can be thrown off balance. Certain conditions can lower the body’s ability to keep the virus in check, making reactivation more likely and sometimes more severe.
Chronic stress is one of the biggest culprits. When we’re under long-term psychological strain—whether from caregiving, demanding jobs, or emotional trauma—the body releases stress hormones like cortisol and epinephrine. These hormones don’t just affect mood or energy; they actively suppress immune function. Research has shown that chronic stress can weaken the activity of T cells and impair the ability of macrophages and dendritic cells to respond effectively to HSV. This means the virus has more room to replicate before the immune system catches up.
Sleep deprivation often goes hand in hand with stress and adds to the problem. Poor sleep disrupts the immune system’s rhythms, making it less responsive. Similarly, a diet lacking in essential nutrients—like vitamin E—can increase oxidative stress and interfere with immune signaling, which worsens the body’s ability to fend off infections, including HSV.
Hormonal shifts and medical treatments can also play a role. Steroids, chemotherapy, and certain autoimmune medications suppress immune responses by design. While they may be necessary for treating other health issues, they also lower the body’s natural defenses against viruses. Hormonal fluctuations, particularly those related to cortisol and related compounds, can enhance HSV replication in nerve cells and impair local immune control.
The result of all these factors is the same: reduced immune surveillance. When the body’s virus-specific T cells and interferon responses are weakened, HSV has more opportunity to reactivate and replicate. This is why many people experience outbreaks during times of high stress, illness, or hormonal change. The virus isn’t stronger—it’s just that the immune system is temporarily distracted or depleted.
Over time, repeated stressors or ongoing immune suppression can increase the frequency and intensity of outbreaks. Understanding these triggers doesn’t mean you can avoid them all—but it can help you recognize patterns and support your immune system in ways that reduce your risk.
Why the Immune System Doesn’t Fully Eradicate HSV
One of the most puzzling things about herpes is its staying power. Even with a fully functioning immune system, HSV can’t be cleared from the body. The virus doesn’t persist because the immune system is weak—it sticks around because it’s evolved to hide extraordinarily well.
The key to HSV’s persistence is latency. Once the virus reaches the neurons in the sensory ganglia, it shuts itself down in a highly controlled way. It stops making the proteins that would normally alert the immune system, instead focusing on producing just one main transcript called LAT (latency-associated transcript). This transcript doesn’t trigger much of a response, allowing the virus to fly under the immune system’s radar. Meanwhile, the viral DNA stays tucked away inside the host cell’s nucleus, with no infectious particles being made.
This silent state makes it extremely difficult for the immune system to detect and target the virus. Normally, immune cells recognize and destroy infected cells by detecting viral proteins displayed on their surface. But HSV-infected neurons don’t display those proteins during latency, so they essentially become invisible.
There’s another layer of complexity: neurons themselves are special. Unlike many other types of cells in the body, neurons aren’t easily replaced. Because they’re so critical—and so difficult to regenerate—the immune system avoids damaging them at all costs. This means that, even when the immune system knows a neuron is infected, it often relies on non-destructive tactics like interferon signaling to suppress the virus rather than killing the host cell.
CD8+ T cells in the ganglia are equipped for this balancing act. They release interferon-gamma to keep the virus quiet, suppressing reactivation without destroying the neuron. Meanwhile, neurons also help manage the situation by downregulating local immune activity. They create a microenvironment that reduces inflammation and prevents excessive immune responses that could lead to tissue damage.
HSV doesn’t just hide—it actively manipulates its environment. It interferes with the body’s antiviral signaling by suppressing important immune pathways, such as those driven by interferons. The virus also promotes exhaustion in HSV-specific T cells, weakening their ability to respond effectively over time. And it mimics host molecules and reduces the visibility of viral markers, making it even harder for the immune system to recognize when the virus begins to stir.
All of these strategies allow HSV to maintain a long-term presence in the body—not because the immune system isn’t trying, but because the virus has become a master of stealth and survival. The immune system adapts, monitors, and suppresses, but HSV always finds a way to slip back into the shadows.
Can Immunity Be Boosted to Fight HSV More Effectively?
While there’s no cure for herpes, the good news is that your immune system isn’t powerless—and there are steps you can take to strengthen its ability to manage the virus. Supporting immune health won’t eliminate HSV, but it can reduce the frequency, severity, and duration of outbreaks, helping you feel more in control.
Lifestyle habits play a foundational role. Regular moderate exercise can enhance immune surveillance, improving the body’s ability to detect and respond to viral activity. Many people find that staying physically active not only boosts overall well-being but also leads to fewer herpes flare-ups.
Sleep and stress are also major players. Poor sleep and chronic stress elevate cortisol levels, which can dampen immune responses, particularly those of virus-specific T cells. On the other hand, getting consistent, restorative sleep and using techniques like mindfulness or therapy to manage stress may reduce the likelihood of reactivation.
Nutrition matters, too. A diet rich in antioxidants and anti-inflammatory foods—think leafy greens, berries, nuts, and oily fish—helps reduce oxidative stress, which is linked to viral reactivation. Supporting your body with the nutrients it needs gives your immune cells the tools to function at their best.
Certain supplements may offer targeted support. Lysine, an amino acid, may help inhibit HSV replication by offsetting arginine, which the virus relies on to reproduce. Vitamin D is another important player—it helps regulate both the innate and adaptive arms of the immune system, and low levels have been associated with increased vulnerability to viral infections, including HSV.
Zinc is also worth noting. Known for its antiviral properties, it supports immune signaling and can be used both preventively and therapeutically. Some topical and vaccine-based approaches even incorporate zinc to enhance immune responses. Probiotics, which support gut health, may also contribute to immune balance, although their direct impact on herpes control is still being explored.
Medical options provide another layer of support. Daily antiviral therapy—using medications like acyclovir or valacyclovir—helps reduce the virus’s activity in the body, which not only lessens symptoms but also lowers the overall burden on the immune system. Fewer outbreaks mean less inflammation and a stronger chance for your immune system to maintain control.
Researchers are also making exciting progress on vaccine development. Some experimental vaccines use weakened versions of the virus, while others rely on advanced delivery systems like nanoparticles to stimulate strong and lasting immunity. These vaccines aim not just to prevent infection but also to help the body mount a more effective response in people already living with HSV.
While boosting immunity isn’t a cure, it’s a meaningful way to reclaim some agency over how HSV affects your life. Small, consistent choices—combined with medical support when needed—can make a significant difference.
Future Directions: Immune-Based Therapies in Research
Although herpes remains incurable, the frontier of immune-based therapies is rapidly expanding. Researchers are exploring bold, innovative ways to help the immune system do what it can’t quite manage on its own: fully control or even eliminate HSV. Much of this progress builds on breakthroughs from cancer and HIV immunotherapy, adapting powerful tools to address the unique challenges of herpes latency and immune evasion.
Therapeutic vaccines are a major focus. These vaccines aren’t designed to prevent initial infection, but rather to help people already living with HSV mount a stronger, more effective immune response. One notable example is T-VEC, originally developed to treat melanoma. It’s a modified HSV-1 virus engineered to express immune-boosting proteins like GM-CSF, which enhance T-cell activation. Its success in cancer has sparked interest in adapting similar approaches to target HSV reservoirs and control outbreaks more effectively.
Other promising candidates include the VC2 strain, a specially engineered HSV-1 vaccine designed to provoke strong CD8+ T-cell responses. This type of response is crucial for suppressing viral reactivation. Meanwhile, nanoparticle-based platforms are being developed to deliver not just viral antigens but also genes that stimulate immunity—such as interleukin-12 or GM-CSF—offering both precision and staying power.
Gene-editing and T-cell engineering are also pushing boundaries. Using technologies like CRISPR/Cas9, scientists are experimenting with ways to make HSV-infected cells more visible to the immune system. Some oncolytic HSV strains have even been modified to express immune-stimulating molecules like CD40L, reshaping the environment around infected or tumor cells and priming them for attack by T cells.
T-cell therapies originally pioneered for cancer and HIV are now being adapted for HSV. This includes transferring custom-designed T-cell receptors that can recognize HSV-infected neurons—even those in latency. Engineered immune cells that produce cytokines like interferon-beta and GM-CSF may also directly activate antiviral responses and help build lasting immune memory.
This cross-pollination of ideas from cancer and HIV research is accelerating progress. Herpes simplex vectors are already used in some cancer trials to deliver powerful immune modulators. Meanwhile, lessons from HIV vaccine research—particularly strategies to sustain memory T-cell responses—are helping inform HSV vaccine development. Even treatments like immune checkpoint inhibitors, which help “unblock” the immune system’s brakes, are being tested in combination with HSV-based therapies to counteract the virus’s stealth tactics.
While these therapies are still largely in the experimental stage, they reflect a deeper shift: a growing understanding that HSV isn’t just a skin-deep problem, but a complex immunological challenge. The future of herpes treatment may lie not just in suppressing outbreaks, but in rewiring the immune system itself to finally tip the balance in our favor.
Living in Partnership With Your Immune System
Herpes can feel like an isolating experience—but the science tells a different story. Behind the scenes, your immune system is constantly working with you, doing its best to keep the virus under control. From the first moments of exposure to the long, quiet stretches of latency, it’s a dynamic partnership between your body and your biology.
While HSV is skilled at staying hidden, it’s not invincible. The immune system, though imperfect in clearing the virus, is powerful in its capacity to contain it. And with the support of healthy habits, medical treatments, and a growing field of immune-based therapies, many people are able to live well with herpes. This journey isn’t about blame or “strong” versus “weak” immunity—it’s about understanding, support, and small, meaningful steps that strengthen your relationship with your health.
If you’d like to stay informed about the latest research, practical tips, and compassionate resources on living with herpes, we invite you to join our mailing list. You’ll receive helpful updates and new articles straight to your inbox—no pressure, just support.
References
Agelidis, A., Koujah, L., Suryawanshi, R., Yadavalli, T., Mishra, Y., Adelung, R., & Shukla, D. (2019). An intra-vaginal zinc oxide tetrapod nanoparticles (ZOTEN) and genital herpesvirus cocktail can provide a novel platform for live virus vaccine. Frontiers in Immunology, 10.
Amin, I., Younas, S., Afzal, S., Shahid, M., & Idrees, M. (2019). Herpes Simplex Virus Type 1 and Host Antiviral Immune Responses: An Update. Viral Immunology.
Balakrishnan, P., Sathish, S., & Saravanan, S. (2024). HIV-encoded gene therapy as anti-cancer therapeutics: A narrative review. Cureus, 16.
Bansode, Y., Chattopadhyay, D., & Saha, B. (2019). Innate immune response in astrocytes infected with herpes simplex virus 1. Archives of Virology, 164, 1433–1439.
Bommareddy, P. K., Patel, A., Hossain, S., & Kaufman, H. L. (2017). Talimogene laherparepvec (T-VEC) and other oncolytic viruses for the treatment of melanoma. American Journal of Clinical Dermatology, 18, 1–15.
Broberg, E., & Hukkanen, V. (2005). Immune response to herpes simplex virus and gamma134.5 deleted HSV vectors. Current Gene Therapy, 5(5), 523–530.
Cao, L., Martin, A., Polakos, N., & Moynihan, J. (2004). Stress causes a further decrease in immunity to herpes simplex virus-1 in immunocompromised hosts. Journal of Neuroimmunology, 156, 21–30.
Chan, T. T., Barra, N., Lee, A. J., & Ashkar, A. (2011). Innate and adaptive immunity against herpes simplex virus type 2 in the genital mucosa. Journal of Reproductive Immunology, 88(2), 210–218.
Chang, J. Y., Balch, C., Puccio, J. A., & Oh, H. (2023). A narrative review of alternative symptomatic treatments for herpes simplex virus. Viruses, 15.
Chen, K.-S., Reinshagen, C., Van Schaik, T. A., Rossignoli, F., Borges, P., Mendonca, N. C., et al. (2023). Bifunctional cancer cell–based vaccine concomitantly drives direct tumor killing and antitumor immunity. Science Translational Medicine, 15.
Chentoufi, A. A., Kritzer, E., Tran, M., Dasgupta, G., Lim, C. H., Yu, D. C., Afifi, R. E., Jiang, X., Carpenter, D., Osorio, N., Hsiang, C., Nesburn, A. B., Wechsler, S. L., & BenMohamed, L. (2011). The Herpes Simplex Virus 1 Latency-Associated Transcript Promotes Functional Exhaustion of Virus-Specific CD8+ T Cells. Journal of Virology, 85, 9127–9138.
Cunningham, A. L., Diefenbach, R. J., Miranda-Saksena, M., Bosnjak, L., Kim, M., Jones, C. A., & Douglas, M. W. (2006). The cycle of human herpes simplex virus infection: virus transport and immune control. The Journal of Infectious Diseases, 194(Suppl 1), S11–S18.
Danastas, K., Miranda-Saksena, M., & Cunningham, A. L. (2020). Herpes simplex virus type 1 interactions with the interferon system. International Journal of Molecular Sciences, 21.
Delwar, Z. M., Tatsiy, O., Chouljenko, D. V., Lee, I.-F., Liu, G., Liu, X., et al. (2023). Prophylactic vaccination and intratumoral boost with HER2-expressing oncolytic herpes simplex virus induces robust and persistent immune response. Vaccines, 11.
Divito, S. J., Cherpes, T. L., & Hendricks, R. L. (2006). A triple entente: Virus, neurons, and CD8+ T cells maintain HSV-1 latency. Immunologic Research, 36, 119–126.
Donaghy, H., Bosnjak, L., Harman, A. N., Marsden, V., Tyring, S. K., Meng, T. C., & Cunningham, A. L. (2008). Role for plasmacytoid dendritic cells in the immune control of recurrent human herpes simplex virus infection. Journal of Virology, 83(4), 1952–1961.
Egan, K. P., Wu, S., Wigdahl, B., & Jennings, S. R. (2013). Immunological control of herpes simplex virus infections. Journal of neurovirology, 19(4), 328–345.
Elftman, M. (2009). Stress-induced glucocorticoids impair dendritic cell function, compromising CD8+ T cell responses to herpes simplex virus.
Fusciello, M., Ylösmäki, E., & Cerullo, V. (2021). Viral nanoparticles: Cancer vaccines and immune modulators. Advances in Experimental Medicine and Biology, 1295, 317–325.
Gill, N., & Ashkar, A. A. (2008). Overexpression of Interleukin-15 compromises CD4-dependent adaptive immune responses against herpes simplex virus 2. Journal of Virology, 83(2), 918–926.
Glaser, R., & Kiecolt-Glaser, J. (1997). Chronic stress modulates the virus-specific immune response to latent herpes simplex virus Type 1. Annals of Behavioral Medicine, 19, 78–82.
Gudmundsdotter, L., Sjödin, A.-P., Boström, A., Hejdeman, B., Theve-Palm, R., Alaeus, A., et al. (2006). Therapeutic immunization for HIV. Springer Seminars in Immunopathology, 28, 221–230.
Ives, A. M., & Bertke, A. S. (2017). Stress hormones epinephrine and corticosterone selectively modulate herpes simplex virus 1 (HSV-1) and HSV-2 productive infections in adult sympathetic, but not sensory, neurons. Journal of Virology, 91.
Jiang, X., Chentoufi, A. A., Hsiang, C., Carpenter, D., Osorio, N., BenMohamed, L., Fraser, N. W., Jones, C., & Wechsler, S. L. (2010). The herpes simplex virus type 1 latency-associated transcript can protect neuron-derived cells from granzyme B-induced apoptosis and CD8 T-cell killing. Journal of Virology, 85, 2325–2332.
Khanna, K. (2004). Active Immunosurveillance by CD8+ T Lymphocytes during Acute and Latent Herpes Simplex Virus-1 Infection.
Khanna, K. M., Bonneau, R. H., Kinchington, P. R., & Hendricks, R. L. (2003). Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity, 18(5), 593–603.
Khanna, K. M., Lepisto, A. J., Decman, V., & Hendricks, R. L. (2004). Immune control of herpes simplex virus during latency. Current opinion in immunology, 16(4), 463–469.
Kobayashi, M., Kim, J.-y., Camarena, V., Roehm, P., Chao, M., Wilson, A. C., & Mohr, I. (2012). A primary neuron culture system for the study of herpes simplex virus latency and reactivation. Journal of Visualized Experiments, 62.
Koff, W. C., & Dunegan, M. A. (1986). Neuroendocrine hormones suppress macrophage-mediated lysis of herpes simplex virus-infected cells. Journal of Immunology, 136, 705–709.
Krishnan, R., & Stuart, P. M. (2021). Developments in Vaccination for Herpes Simplex Virus. Frontiers in microbiology, 12, 798927.
Kusnecov, A., Grota, L. J., Schmidt, S., Bonneau, R. H., Sheridan, J. F., Glaser, R., & Moynihan, J. A. (1992). Decreased herpes simplex viral immunity and enhanced pathogenesis following stressor administration in mice. Journal of Neuroimmunology, 38, 129–137.
Liu, T., Khanna, K. M., Chen, X., Fink, D. J., & Hendricks, R. L. (2000). CD8+ T cells can block herpes simplex virus type 1 reactivation from latency in sensory neurons. The Journal of Experimental Medicine, 191, 1459–1466.
Low-Calle, A. M., Prada-Arismendy, J., & Castellanos, J. E. (2014). Study of interferon-β antiviral activity against Herpes simplex virus type 1 in neuron-enriched trigeminal ganglia cultures. Virus research, 180, 49–58.
Morrison, L. A., & Knipe, D. M. (1997). Contributions of antibody and T cell subsets to protection elicited by immunization with a replication-defective mutant of herpes simplex virus type 1. Virology, 239(2), 315–326.
Mukhopadhyay, A., Indra, S., Ghosh, J., Biswas, S., Palit, P., & Chattopadhyay, D. (2024). Herpes simplex virus-mediated skin infections: cytokines and its interplay. Exploration of Immunology.
Peng, T., Zhu, J., Klock, A., Phasouk, K., Huang, M.-L., Koelle, D. M., Wald, A., & Corey, L. (2009). Evasion of the mucosal innate immune system by herpes simplex virus type 2. Journal of Virology, 83(24), 12559–12568.
Perry, C. L., Banasik, B. N., Gorder, S. R., Xia, J., Auclair, S., Bourne, N., & Milligan, G. (2016). Detection of herpes simplex virus type 2 (HSV-2)-specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection. Journal of Immunological Methods, 439, 1–7.
Schenkel, J. M., Fraser, K. A., Beura, L. K., Pauken, K. E., Vezys, V., & Masopust, D. (2014). Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science, 346(6205), 98–101.
Sheridan, P. A., & Beck, M. A. (2008). The immune response to herpes simplex virus encephalitis in mice is modulated by dietary vitamin E. The Journal of Nutrition, 138(1), 130–137.
Srivastava, R., Dervillez, X., Khan, A. A., Chentoufi, A. A., Chilukuri, S., Shukr, N., Fazli, Y., Ong, N. N., Afifi, R. E., Osorio, N., Geertsema, R., Nesburn, A. B., Wechsler, S. L., & BenMohamed, L. (2016). The Herpes Simplex Virus Latency-Associated Transcript Gene Is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8+ T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits. Journal of virology, 90(8), 3913–3928.
Srivastava, R., Khan, A. A., Chilukuri, S., Syed, S. A., Tran, T. T., Furness, J. N., Bahraoui, E., & BenMohamed, L. (2017). CXCL10/CXCR3-dependent mobilization of herpes simplex virus-specific CD8+ TEM and CD8+ TRM cells within infected tissues allows efficient protection against recurrent herpesvirus infection and disease. Journal of Virology, 91.
St. Leger, A. J., & Hendricks, R. L. (2011). CD8+ T cells patrol HSV-1-infected trigeminal ganglia and prevent viral reactivation. Journal of NeuroVirology, 17, 528–534.
Stanfield, B. A., Rider, P. J. F., Caskey, J. R., Del Piero, F., & Kousoulas, K. G. (2018). Intramuscular vaccination of guinea pigs with the live-attenuated human herpes simplex vaccine VC2 stimulates a transcriptional profile of vaginal Th17 and regulatory Tr1 responses. Vaccine, 36(20), 2842–2849.
Steiner, I., & Kennedy, P. G. (1995). Herpes simplex virus latent infection in the nervous system. Journal of neurovirology, 1(1), 19–29.
Suazo, P. A., Ibáñez, F. J., Retamal-Díaz, A., Paz-Fiblas, M. V., Bueno, S. M., Kalergis, A. M., & González, P. A. (2015). Evasion of early antiviral responses by herpes simplex viruses. Mediators of Inflammation, 2015, Article ID 593757.
Suvas S, Azkur AK, Rouse BT. Qa-1b and CD94-NKG2a interaction regulate cytolytic activity of herpes simplex virus-specific memory CD8+ T cells in the latently infected trigeminal ganglia. J Immunol. 2006 Feb 1;176(3):1703-11.
Tenser, R. B., Edris, W. A., & Hay, K. A. (1993). Neuronal control of herpes simplex virus latency. Virology, 195(2), 337–347.
Uchakin, P. N., Parish, D. C., Dane, F. C., Uchakina, O. N., Scheetz, A. P., Agarwal, N. K., & Smith, B. E. (2011). Fatigue in medical residents leads to reactivation of herpes virus latency. Interdisciplinary Perspectives on Infectious Diseases, 2011.
Uche, I. K., Stanfield, B. A., Rudd, J. S., Kousoulas, K., & Rider, P. J. F. (2022). Utility of a recombinant HSV-1 vaccine vector for personalized cancer vaccines. Frontiers in Molecular Biosciences, 9.
Uyangaa, E., Patil, A. M., & Eo, S. K. (2014). 46: Distinct upstream role of type I IFN signal to hematopoietic stem cell-derived leukocytes and resident cells for connected recruitment of Ly-6C high monocytes and NK cells via CCL2–CCL3 cascade to restrict CNS-invasion of herpes simplex virus in mucosal tissues. Cytokine, 70, 39.
van Lint, A. L., Kleinert, L., Clarke, S. R., Stock, A. T., Heath, W. R., & Carbone, F. R. (2005). Latent infection with herpes simplex virus is associated with ongoing CD8+ T-cell stimulation by parenchymal cells within sensory ganglia. Journal of Virology, 79, 14843–14851.
Wang, R., Chen, J., Wang, W., Zhao, Z., Wang, H., Liu, S., et al. (2022). CD40L-armed oncolytic herpes simplex virus suppresses pancreatic ductal adenocarcinoma. Journal for Immunotherapy of Cancer, 10.
Weiss, K. A., Petro, C. D., Herold, B. C., & Jacobs, W. R. (2016). Herpes simplex virus-2 ΔgD vaccination primes robust cellular immunity with memory Th17 cell recall following challenge. The Journal of Immunology, 196(Suppl. 1), 146.3.
Yasukawa, M., Ochi, T., & Fujiwara, H. (2011). Adoptive T-cell immunotherapy using T-cell receptor gene transfer: Aiming at a cure for cancer. Immunotherapy, 3(2), 135–140.
Zhu, J., & Miner, M. D. (2024). Local power: The role of tissue-resident immunity in human genital herpes simplex virus reactivation. Viruses, 16(7).
