Reactivation Of HSV Research Articles

Herpes Simplex Epithelial Keratitis and Contact lens: A Case Report

Herpes simplex virus keratitis is an ocular infection arising from the reactivation of HSV; if not promptly addressed, it can lead to diminished visual acuity and potential blindness in the affected eye. The sight-threatening aspects of this infection are primarily associated with the development of scarring and opacity. A 22-year-old woman, an otherwise healthy contact lens wearer, sought medical attention with complaints of painful, red, and photophobic eyes. Upon examination, a dendritic ulcer was observed on the right eye, accompanied by toxic keratopathy in both eyes. The treatment regimen that was implemented consisted of valacyclovir and ocular lubrication. The disruption of the host's natural immunological barriers, exacerbated by suboptimal contact lens handling, paved the way for subsequent dendritic ulceration. This occurrence was instigated by the reactivation of the herpes simplex virus, underscoring the critical importance of timely intervention.

Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV

Herpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients.Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivation animal models (intravaginal guinea pig HSV-2 infection model and ocular mouse HSV-1 infection model) is presented. Intermittent therapy of infected animals with 4–7 cycles of IM-250 during latency silences subsequent recurrences analyzed up to 6 months. In contrast to common experience, our studies show that the latent reservoir is indeed accessible to antiviral therapy altering the latent viral reservoir such that reactivation frequency can be reduced significantly by prior IM-250 treatment.We provide evidence that antiviral treatment during HSV latency can reduce future reactivation from the latent reservoir, supporting a conceptual shift in the antiviral field, and reframing what is achievable with respect to therapy of latent neuronal HSV infections.

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

Fulminant Herpes Pneumonia Postaortic Surgery with Known Ankylosing Spondylitis.

Herpes simplex virus (HSV) pneumonitis is rare after cardiac surgery. A 36-year-old gentleman with ankylosing spondylitis underwent emergency surgery for a complex aortic aneurysmal disease. Preoperative treatment of aortitis with antitumor necrosis factor and steroid medication and surgical stress including cardiopulmonary bypass potentially created an immunosuppressive state and reactivation of undiagnosed HSV. Rapid HSV pneumonia ensued, culminating in fulminant organ failure and mortality. HSV pneumonia should be considered postoperatively in patients with severe respiratory distress, especially if immunocompromised.

La paralysie faciale périphérique a frigore

Idiopathic peripheral facial palsy, also named Bell's palsy, is the most common cause of peripheral facial palsy in adults. Although it is considered as a benign condition, its social and psychological impact can be dramatic, especially in the case of incomplete recovery. The main pathophysiological hypothesis is the reactivation of HSV 1 virus in the geniculate ganglia, leading to nerve edema and its compression through the petrosal bone. Patients experience an acute (less than 24 hours) motor deficit involving ipsilateral muscles of the upper and lower face and reaching its peak within the first three days. Frequently, symptoms are preceded or accompanied by retro-auricular pain and/or ipsilateral face numbness. Diagnosis is usually clinical but one should look for negative signs to eliminate central facial palsy or peripheral facial palsy secondary to infectious, neoplastic or autoimmune diseases. About 75% of the patients will experience spontaneous full recovery, this rate can be improved with oral corticotherapy when introduced within the first 72 hours. To date, no benefit has been demonstrated by adding an antiviral treatment. Hemifacial spasms (involuntary muscles contractions of the hemiface) or syncinesia (involuntary muscles contractions elicited by voluntary ones, due to aberrant reinnervation) may complicate the disease's course. Electroneuromyography can be useful at different stages: it can first reveal the early conduction bloc, then estimate the axonal loss, then bring evidence of the reinnervation process and, lastly, help for the diagnosis of complications.

Radiation Exposure and Bell’s Palsy: A Hypothetical Association

Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. It accounts for 60 to 75% of all cases of unilateral facial paralysis. The main mechanisms to induce BP remain unclear, but infection, ischemic condition and immunodeficiency may contribute to the development of Bell's palsy. Accumulating evidence has shown several factors can trigger the reactivation of latent HSV including psychological stressors, physical stressors and immunosuppression. Ionization and non-ionization radiations are of importance of physical stressors. Some data have shown radiation can reactivate HSVs. Based on preliminary studies showing radiation reactivation of HSVs, we aimed to hypothesize radiation (in both forms of ionization and non-ionization) may cause Bell's palsy. In the future, the role of radiotherapy, radiofrequency radiation from mobile phones and wireless devices in HSV reactivation and Bell's palsy should be investigated.

Concurrent Reactivation of VZV and HSV-2 in a Patient with Uncontrolled Diabetes Mellitus: A Case Report

Background: Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) and varicella zoster virus (VZV) are neurotropic herpesviruses that cause vesicular mucocutaneous eruptions. They both establish latency in peripheral ganglia and can reactivate to cause episodic outbreaks. HSV occurs more often in the young and may reactivate frequently. VZV reactivation is associated with advancing age due to a decline in the VZV-specific T cell population. While both viruses have been isolated from the same sensory ganglia, they rarely cause simultaneous disease. In most of these cases the viruses have been isolated at different body sites in immunocompromised hosts. However, clinical disease with concurrent detection of both HSV and VZV from the same anatomic location has been described. In a prior study of dual positive specimens, a lower PCR cycle threshold (Ct) was consistently observed for VZV, suggesting that zoster caused subsequent reactivation of HSV. Case presentation: Here we describe the case of a 64-year-old patient with uncontrolled diabetes who presented with painful penile ulcers and a dermatomal, crusted, left lower abdominal rash. His penile ulcers were positive for both HSV-2 and VZV by PCR. Ct data suggested that primary zoster led to secondary genital HSV-2. Hyperglycemia is known to cause reversible T cell dysfunction and was the likely precipitating factor for the patient’s illness, which responded to oral valacyclovir. Conclusion: To our knowledge this is the first report of diabetes-related concurrent herpesvirus reactivation. Clinicians should consider the possibility of simultaneous HSV and VZV infection in patients who present with dermatomal zosteriform lesions since higher antiviral doses are recommended for herpes zoster as compared to herpes simplex.

Palsy – Treatment Efficacy by Drugs and Interferential Current Therapy

Bell's palsy also term idiopathic facial palsy has uncertain etiology. Controversy in management issue makes “Bell's palsy” a novel disorder. Although majority of patients regain their normal or near normal facial motor function, certain percentage of sufferers shows incomplete motor function recovery of peripheral VII cranial nerve with or without troublesome synkinesis. At this context, a randomized clinical trial was made to see the efficacy of interferential current along with medical management for therapeutic benefit and to prevent long term sequallae. Some other important issue like natural history, reactivation of HSV – Type 1 viral etiology, medical, surgical and acupuncture treatment were reviewed.

The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons.

The alphaherpesviral envelope protein pUS9 has been shown to play a role in the anterograde axonal transport of herpes simplex virus 1 (HSV-1), yet the molecular mechanism is unknown. To address this, we used an in vitro pulldown assay to define a series of five arginine residues within the conserved pUS9 basic domain that were essential for binding the molecular motor kinesin-1. The mutation of these pUS9 arginine residues to asparagine blocked the binding of both recombinant and native kinesin-1. We next generated HSV-1 with the same pUS9 arginine residues mutated to asparagine (HSV-1pUS9KBDM) and then restored them being to arginine (HSV-1pUS9KBDR). The two mutated viruses were analyzed initially in a zosteriform model of recurrent cutaneous infection. The primary skin lesion scores were identical in severity and kinetics, and there were no differences in viral load at dorsal root ganglionic (DRG) neurons at day 4 postinfection (p.i.) for both viruses. In contrast, HSV-1pUS9KBDM showed a partial reduction in secondary skin lesions at day 8 p.i. compared to the level for HSV-1pUS9KBDR. The use of rat DRG neuronal cultures in a microfluidic chamber system showed both a reduction in anterograde axonal transport and spread from axons to nonneuronal cells for HSV-1pUS9KBDM. Therefore, the basic domain of pUS9 contributes to anterograde axonal transport and spread of HSV-1 from neurons to the skin through recruitment of kinesin-1. Herpes simplex virus 1 and 2 cause genital herpes, blindness, encephalitis, and occasionally neonatal deaths. There is also increasing evidence that sexually transmitted genital herpes increases HIV acquisition, and the reactivation of HSV increases HIV replication and transmission. New antiviral strategies are required to control resistant viruses and to block HSV spread, thereby reducing HIV acquisition and transmission. These aims will be facilitated through understanding how HSV is transported down nerves and into skin. In this study, we have defined how a key viral protein plays a role in both axonal transport and spread of the virus from nerve cells to the skin.

Immunological control of herpes simplex virus infections

Herpes simplex virus type 1 (HSV-1) is capable of causing a latent infection in sensory neurons that lasts for the lifetime of the host. The primary infection is resolved following the induction of the innate immune response that controls replication of the virus until the adaptive immune response can clear the active infection. HSV-1-specific CD8+ T cells survey the ganglionic regions containing latently infected neurons and participate in preventing reactivation of HSV from latency. The long-term residence and migration dynamics of the T cells in the trigeminal ganglia appear to distinguish them from the traditional memory T cell subsets. Recently described tissue resident memory (TRM) T cells establish residence and survive for long periods in peripheral tissue compartments following antigen exposure. This review focuses on the immune system response to HSV-1 infection. Particular emphasis is placed on the evidence pointing to the HSV-1-specific CD8+ T cells in the trigeminal belonging to the TRM class of memory T cells and the role of TRM cells in virus infection, pathogenesis, latency, and disease.

Herpes Simplex

Herpes Simplex

Impairment in reactivation of a latency associated transcript (LAT)-deficient HSV-2 is not solely dependent on the latent viral load or the number of CD8 + T cells infiltrating the ganglia

The HSV latency-associated transcript (LAT) is abundantly expressed during virus latency. Previous studies have shown that the latent viral load and CD8 + T cells in ganglia influence the rate of reactivation of HSV. While LAT is important for efficient reactivation and establishment of latency, it is uncertain how LAT affects either the HSV latent viral load or CD8 + T cell infiltration of ganglia. We infected mice with LAT-deficient or LAT-restored HSV-2 at a wide range of inocula. We found that the reduced rate of spontaneous ex-vivo reactivation of the LAT-deficient virus was not associated with a higher number of CD8 + T cells in the ganglia. Reactivation rates were lower for LAT-deficient than LAT restored HSV-2 even when the latent viral loads were similar, indicating that differences in reactivation were not solely dependent on the latent viral load. Therefore, LAT likely has additional functions important for reactivation.

Spontaneous Reactivation of Herpes Simplex Virus Type 1 in Latently Infected Murine Sensory Ganglia

Careful studies of mouse trigeminal ganglia (TG) latently infected with herpes simplex virus type 1 (HSV-1) indicate the presence of productive cycle viral gene products and persistent immune response, suggesting ongoing spontaneous viral reactivation in these tissues. In the present study we set out to determine whether infectious virus is present in murine TG latently infected with HSV-1 (KOS). At 37 days after ocular inoculation we found a small amount of infectious virus in ca. 6% of latently infected murine TG. Furthermore, the amount of infectious virus that we detected (PFU per viral antigen-positive neuron) was similar to that detected in acutely infected ganglia. We conclude that spontaneous reactivation of infectious HSV-1 occurs in the mouse TG and is likely the principle cause of viral protein expression in these tissues. We next examined the role of latency-associated transcript (LAT) in spontaneous ganglionic reactivation by examining ganglia latently infected with KOS dlLAT1.8, a LAT deletion virus. Through the use of immunocytochemistry we found that KOS dlLAT1.8 had a rate of spontaneous ganglionic reactivation very similar to that of HSV-1 (KOS). Studying spontaneous ganglionic reactivation of HSV in the mouse TG allows a direct study of viral reactivation from latently infected neurons without the potential confounders and complicating downstream events that accompany the study of viral reactivation by explantation or peripheral viral shedding. Since most cases of human viral shedding and reactivation are not associated with a known trigger, spontaneous ganglionic reactivation of HSV-1 may be a better model of human disease than existing models.

Combination therapy with alemtuzumab and pentostatin is effective and has acceptable toxicity in patients with T-lymphoid neoplasms

7037 Background: The development of effective therapeutic strategies for T-lymphoid neoplasms has been difficult partly due to the paucity of clinical trials. These neoplasms are generally refractory to traditional chemotherapy regimens. Alemtuzumab and pentostatin have response rates of 50% to 65% when used individually to treat various T-cell leukemias and lymphomas. However, most responses are partial and of limited duration. Methods: We have treated 20 patients (pts) with T-lymphoid malignancies (11 T-PLL, 1 ATL, 1 PTCL, 2 T- ALL, 3 γd-T cell hepatosplenic lymphoma, 2 T-LGL) with a combination of alemtuzumab 30 mg IV, 3 times weekly for up to 3 months and pentostatin 4 mg/m2 weekly×4 followed by alternate weekly administration for up to 6 months. Prophylactic antibiotics were administered during the treatment and for 2 months after its completion. Results: The median age of pts was 57 yrs (range, 22 –79 yrs), median WBC was 43.9×109/L (range 0.6 –279.5 x109/L), and median serum β2M was 4.1 mg/L (range, 1.7 –10.8 mg/L). Four pts had splenomegaly, and 6 lymphadenopathy. Thirteen had prior therapy (median 2). Twelve pts have responded (10 CR, 2 PR) for an overall response rate of 60% (including 8 of 11 T-PLL, 1 of 1 ATL, 0 of 2 T-ALL, 2 of 3γd-T cell hepatosplenic lymphoma, 0 of 1 PTCL and 1 of 2 T-LGL). Monoclonal T-cell receptor chain gene rearrangements were detected by PCR in 18 pts and became negative in 5 of 7 evaluable pts in CR. Median response duration has not been reached (range, 0 to 78 weeks). 3 pts have proceeded to allogeneic stem cell transplant, 4 (1 with ATL, 2 with T-PLL, and 1 with T-LGL) have died from disease progression after a response, and 8 were refractory to therapy. Opportunistic infections included reactivation of CMV in 7 pts, reactivation of HSV in 1 pt, recurrence of pre-existing Serratia pneumonia in 1 pt and Aspergillus pneumonia in 2 pts. Unexplained, marked and sustained pancytopenia occurred in 2 pts. Other toxicities were mainly grade 1 and 2 and included nausea, fever, edema, and shortness of breath. Conclusions: The combination of alemtuzumab and pentostatin is feasible and effective in T-cell neoplasms. Although infections including CMV reactivation are a concern, they may be minimized with adequate prophylactic antibiotic therapy. No significant financial relationships to disclose.

A Herpes simplex virus-1 fatal encephalitis following chemo-radiotherapy, steroids and prophylactic cranial irradiation in a small cell lung cancer patient

Approximately 20-25% of patients with limited small cell lung cancer (SCLC) can be cured with an aggressive approach (chest radiation concomitant with chemotherapy) followed by prophylactic cranial irradiation (PCI) to a total dose of 30-36Gy with 3-2Gy per fraction, five fractions per week. Steroid prophylactic therapy with dexamethasone is usually prescribed during PCI to minimize acute radiation induced brain oedema. This approach may induce an immunosuppressive condition leading to a reactivation of an endogenous latent Herpes simplex virus and severe or fatal acute encephalitis may occur as our report will show. A 55-year-old man affected by locally advanced SCLC was referred to our institution after four cycles of chemotherapy with a good partial remission. Chest radiation started concomitantly with two cycles of chemotherapy followed by PCI 36Gy total dose and dexamethasone 8mg i.m. daily. Fifteen days after PCI completion the patient developed acute neurological symptoms of confusion, cognitive impairment, fever with shaking requiring severe sedation therapy. Twenty-five days later MRI T1 weighted images showed haemorrhagic streaked lines on cortical convolutions of the right cerebral hemisphere and diffuse oedema suggestive of herpetic encephalitis. The DNA consensus test on cerebrospinal fluid (CSF) was positive for Herpes simplex virus 1 infection (HSV-1). A diagnosis of herpetic encephalitis HSV-1 was made. Antiviral therapy with high doses of acyclovir was prescribed but symptoms did not ameliorate leading to a comatose state. The patient died 55 days after the end of PCI. In eligible SCLC patients, PCI is an important part of an aggressive therapeutic approach that improves overall and disease free survival decreasing the risk of relapse in the brain. A primary infection or a reactivation of an endogenous latent HSV in brain parenchyma under steroid therapy concomitant to brain irradiation may compromise these benefits.

Latency and reactivation of HSV: role of LAT and ICP0

The virus herpes simplex type 1 (HSV1) is characterized by its ability to become latent within the nervous system after a primary infection that is almost always located into the oral mucosa. Several factors may trigger HSV1 reactivation, thus inducing recurrences, which are mostly located on the lips (cold sore), sometimes in the eye (most frequently into the cornea) and, exceptionally, in the central nervous system (meningitis and encephalitis). Considering the frequency of the HSV1 infection in the general population and the associated morbidity (approximately 15 % of people have relapsing cold sores, and 90,000 French people have an history of ocular herpes disease), many research projects are focused on the biologic patterns regulating the switch between viral latency and reactivation. In spite of the multitude of scientific publications, numerous points are still poorly understood. However, molecular biology allowed consequent progress. The putative roles of Latency Associated Transcripts (LAT), until recently considered as the only viral transcripts during viral latency, are now better identified. It is now obvious that LAT interact with other viral partners. The transcripts encoding ICP0, a viral protein which is known to have a key role in the reactivation process, could be involved in this phenomenon, since their properties are opposite to those of LAT. The couple LAT-ICP0 transcripts could thus represent the molecular aspect of the classic opposition between latency and reactivation of HSV1.

Combination Therapy with Alemtuzumab and Pentostatin Is Effective and Has Acceptable Toxicity in Patients with T-Lymphoid Neoplasms.

The development of effective therapeutic strategies for T-lymphoid neoplasms has been difficult partly due to their rarity and paucity of clinical trials. These neoplasms are generally refractory to traditional chemotherapy regimens and novel therapeutic strategies are needed. Alemtuzumab and pentostatin have response rates of 50% to 65% when used individually to treat various T-cell leukemias and lymphomas. However, most responses are partial and of limited duration. Immunosuppression and risk of opportunistic infections are their principal overlapping toxicities. We have treated 17 patients with T-lymphoid malignancies (10 T-PLL, 1 ATL, 2 T-ALL, 2 γδ-T cell hepatosplenic lymphoma, 2 T-LGL) with a combination of alemtuzumab 30 mg IV, 3 times weekly for up to 3 months and pentostatin 4 mg/m2 weekly × 4 followed by alternate weekly administration for up to 6 months. Prophylactic antibiotics including valacyclovir, fluconazole, and trimethoprim/sulfamethoxazole (or equivalents) were administered during the treatment and for 2 months after its completion. The median age of patients was 57 years (range 22 – 79 years), median white blood count was 54.1 × 109/L (range 0.6 – 279.5 ×109/L), and median serum β2M was 4.0 mg/L (range, 1.7 – 10.8 mg/L). Four patients had splenomegaly (1 to 5 cm), and 5 lymphadenopathy. Eleven had prior therapy (median 2, range 1 to 6 regimens). Eleven patients have responded (8 CR, 3 PR) for an overall response rate of 65% (including 8 of 10 T-PLL, 1 of 1 ATL, 0 of 2 T-ALL, 1 of 2 γδ-T cell hepatosplenic lymphoma and 1 of 2 T-LGL). Monoclonal T-cell receptor chain gene rearrangements were detected by PCR in 16 patients and became negative in 5 of 7 evaluable patients in CR. Median response duration has not been reached (range 0 to 78 weeks). Three patients have proceeded to allogeneic stem cell transplant, 4 (1 with ATL, 2 with T-PLL, and 1 with T-LGL) have died from disease progression after a response, and 6 were refractory to therapy. Opportunistic infections included reactivation of CMV in 6 patients (no disease), reactivation of HSV in 1 patient, recurrence of pre-existing Serratia pneumonia in 1 patient and Aspergillus pneumonia in 2 patients. Unexplained, marked and sustained pancytopenia occurred in 2 patients, 1 with T-LGL and 1 with T-PLL. Other toxicities were mainly grade 1 and 2 and included nausea, fever, fatigue, infusion reactions, edema, and shortness of breath. The combination of alemtuzumab and pentostatin is feasible and effective in T-cell neoplasms. Although infections including CMV reactivation are a concern, they may be minimized with adequate prophylactic antibiotic therapy. [Display omitted]

Combined Therapy with Alemtuzumab and Pentostatin Is Feasible and Effective in T- Lymphoprolifertive Disorders.

Mature T-cell lymphoid neoplasms are clonal proliferation of post-thymic T-cells, which are generally refractory to traditional chemotherapy regimens. The prognosis for most patients with these disorders, particularly those with relapsed disease, is poor. New treatment strategies are urgently needed. Alemtuzumab and pentostatin have been used as single agents in various T-cell neoplasms with response rates of up to 75% and 50%, respectively. Immunosuppression and opportunistic infections are the principal overlapping toxicities. We have treated 9 patients with T-lymphoid malignancies (5 T-PLL, 1 ATL, 1 γδ-T-cell hepatosplenic lymphoma, 2 T-LGL) on a phase II study of alemtuzumab 30 mg IV three times weekly for up to 3 months with concomitant pentostatin 4 mg/m2 weekly x 4 followed by alternate weekly administration for up to 6 months. Prophylactic antibiotics including valcyclovir, trimethoprim/sulfamethoxazole, and fluconazole were administered during therapy and for 2 months after completion. Median age of patients was 57 years (range 25–80 years), median WBC was 78.5 x 109/L (range 0.7 – 279.5 x109/L), median serum β2M was 4.1 mg/L (2.7 – 10.8 mg/L). Six patients had splenomegaly (1 – 6 cm), and 3 lymphadenoapthy. Six had received prior therapy (median 5, range 1 to 6 regimens). To date, 6 of 8 evaluable patients have responded (5 CR, 1PR). One patient who had failed both single agent pentostatin and single agent alemtuzumab achieved CR with the combination. Monoclonal T-cell receptor gamma chain gene rearrangements were detected by PCR in all patients and became negative in 3 of 5 evaluable responding patients. Median response duration is 5+ months (range 2 – 6+ months). Two patients proceeded to an allogeneic stem cell transplant, 2 (1 with ATL and 1 with T-LGL) have died from disease progression after a response, 2 are alive and disease-free, and 2 were refractory to therapy. Opportunistic infections have included reactivation of CMV and HSV in one patient, recurrence of pre-existing Serratia pneumonia in 1 patient and Aspergillus pneumonia in 1 patient. We conclude that the combination of alemtuzumab and pentostatin is effective in T-cell neoplasms; infections can be prevented with prophylactic antibiotic therapy and close monitoring of patients.

Herpes Simplex Virus Encephalitis During Suppressive Therapy With Acyclovir in a Premature Infant

Cutaneous herpes simplex virus type 2 (HSV-2) infection was recognized at 19 days of age in a 1415-g female infant born at 31 weeks of gestation. Cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) was negative, and MRI of the brain was normal. After a 14-day course of high-dose intravenous acyclovir, the infant developed a cutaneous recurrence at 38 days of age. CSF HSV PCR again was negative. She was subsequently begun on oral acyclovir to prevent cutaneous reactivation of HSV. At 3 months of age, the infant developed HSV encephalitis as manifested by fever, seizures, abnormal CSF indices, abnormal brain MRI, and positive CSF HSV PCR. No cutaneous disease was present. It is not known whether the HSV encephalitis in our patient represented reactivation of previously unrecognized central nervous system infection or new onset of central nervous system disease as a result of spread from other tissue or site to the brain. The failure of oral acyclovir to prevent such an occurrence, however, highlights gaps in our understanding of the pathogenesis of neonatal HSV disease and questions the use of acyclovir suppression to prevent neurologic sequelae.

Opportunisticheskaya gerpes-virusnaya infektsiya v patogeneze uveitov u detey s yuvenil'nym khronicheskim artritom

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