Reactivation from Latency and Recurrence of HSV Infections Due to Impaired Th-1 Cytokines

HSV infections are ubiquitous and cause significant morbidity worldwide. After a productive primary HSV infection, the virus gets cleared off spontaneously in the majority of the individuals. However, in a proportion of patients, the virus establishes a chronic state known as latent infections in the neurons. In general HSV-1 causes lesions above the waist in contrast HSV-2 below waist although vice versa infections are not uncommon. During latency, the HSV infects the dorsal root ganglion but it remains almost silent in terms of replication. Upon a poorly defined trigger or insult, HSV gets reactivated i.e the virus replicate enormously (prodrome phase) and migrate towards the same neuro dermatome through which it entered and cause agonizing painful necrotizing lesions of genitals or mouth. It has been a myth about what is such trigger or insult that provokes recrudescence. It has been postulated that conditions such as stress, Catamenia (menstrual cycle), fever, exposure to sunlight, radiation and trauma either alone or in the combination of multiple factors are believed to be the cause of recurrence. In this paper, we report a novel mechanism that a decrease of normal Th-1 cytokine milieu may trigger the HSV reactivation and recurrent infection. K. Vasanthi 1 , M. Dhanalakshmi 1 , V. Pugalendhi 2 and Elanchezhiyan Manickan 1 1Department of Microbiology, Dr. ALM PG IBMS, University of Madras, Taramani, Chennai, India 2Voluntary Health Science, Taramani, Chennai, India. Submission: 21 July 2017 Accepted: 30 July 2017 Published: 30 August 2017 www.ijppr. humanjournals.com Citation: Elanchezhiyan Manickan et al. Ijppr.Human, 2017; Vol. 10 (1): 1-11. 2 INTRODUCTION Herpes Simplex Viruses (HSV) infections are ubiquitous and they cause infections ranging from mild gingivostomatitis to life threatening encephalitis in immunocompromised individuals 1 . HSV consists of two types namely HSV-1 and HSV-2 and these viruses upon primary infection they reach the nervous system via the nerve ending. In the nervous system, they migrate towards the dorsal root ganglion and HSV-1 normally encroach trigeminal ganglion and HSV-2 the lumbosacral ganglion. At the periphery, HSV causes lytic infections and in the ganglion, they undergo some metamorphosis and acquire a special chronic and silent type of infection known as latent infection 2 . Once the organism causes latent infection in the neurons the virus stays in the body for the rest of the life of the patient 3 . During latent infection, the virus shuts down almost all its genes and up-regulates a new gene cluster called latency associated transcripts (LATs) which are the only transcripts found at this time. Lytic infections are prone to the immune attack of the virus and elimination. In contrast, latent infection provides a survival advantage to the virus since it remains asymptomatic and evade immune surveillance. The exact genes responsible for latency is complex. The elements surrounding the ICP-0 gene bind with a host protein called neuronal restrictive silencing factor (NRSF). This binding leads to histone deacetylation upstream of ICP-0 gene which prevents the transcription for a lytic infection 4 . In general, HSV-1 causes infections above waist and HSV-2 below waist though vice versa is also common. Though HSV-1 and HSV-2 are antigenically distinct and variable tissue tropism their trigger mechanism and reactivation appears to similar. Once triggered they undergo a lytic replication and migrate centrifugally from the CNS to the exactly same neuro dermatome through which they entered and cause devastating psychosomatic herpes disease. While spatial regulation of viral proteins involved in the disease development cellular factors such as cytokines predominantly determines the outcome of the diseases. During HSV infections, Th-1cytokines namely IFNγ, IL-2, and TNF-α are beneficial to host while Th-2 cytokines namely IL-10 and IL-4 are not. This is because HSV infections are intracellular and only CMI can identify and destroy them 5 . Th-1 cells, in general, promote CMI mounted by T cells. Th-2 cells generally govern the humoral immunity (HI) i.e. antibody mediated immunity. Antibodies are better to eliminate all the circulating viruses in the body fluids but their intracellular action is minimal and hence not beneficial to the host 5 . This up/down regulation of either Th-1 or Th-2 cytokine determines the outcome of HSV mediated disease. www.ijppr. humanjournals.com Citation: Elanchezhiyan Manickan et al. Ijppr.Human, 2017; Vol. 10 (1): 1-11. 3 Since T helper cytokines are such pivotal in determining the disease outcome we made an attempt to study its role of cytokines in HSV latency. For this, we collected serum samples from patients suffering from active HSV lesion and subjected for Th-1 and Th-2 cytokine estimation. MATERIALS AND METHODS