J Infect 2006 May 19; (Read article online)

Panasiti V, Devirgiliis V, Borroni RG, Spataro A, Melis L, Petrella MC, Pala S

Herpes simplex virus type 2 (HSV-2) infection was one of the first opportunistic infections identified among patients with AIDS. In the literature there are many data suggesting that the natural history of HSV-2 infection is altered in HIV-HSV-2 co-infected patients. Furthermore, a relationship between HIV seropositivity and HBV infection because of their analogous way of transmission is also described. We report the case of a 37-year-old patient who suffered from multiple painful ulcerative lesions of the perianal region. Laboratory examination showed positivity for HIV and HBV infections. In HIV-positive patients perianal HSV-2 can have atypical manifestations, especially if co-infection by Candida albicans occurs.

Bioorg Med Chem 2006 May 17; (Read article online)

Goodell JR, Madhok AA, Hiasa H, Ferguson DM

The discovery of new non-nucleoside antiviral compounds is of significant and growing interest for treating herpes virus infections due to the emergence of nucleoside-resistant strains. Using a whole cell virus-induced cytopathogenic assay, we tested a series of substituted triaryl heterocyclic compounds including acridones, xanthones, and acridines. The compounds which showed activity against Herpes Simplex-1 and/or Herpes Simplex-2 were further assayed for inhibition of topoisomerase activity to gain insight into the mechanism of action. The results indicate that the acridine analogs bearing substituted carboxamides and bulky 9-amino functionalities are able to inhibit herpes infections as well as inhibit topoisomerase II relaxation of supercoiled DNA. Given the mechanism of action of amsacrine (a closely related, well-studied 9-amino substituted acridine), the compounds were further tested in a DNA topoisomerase II cleavage assay to determine if the compounds function as poisons. The results show that the acridines synthesized in this study function through a different mechanism to that of amsacrine, most likely by blocking topoisomerase binding to DNA (akin to that of aclarubicin). This not only suggests a unique mechanism of action in treating herpes virus infections, but also may be of great interest in the development of anticancer agents that target topoisomerase II activity.

Pain Med 2006 May-Jun; 7(3): 243-9 (Read article online)

Weiner DK, Schmader KE

Objective. To describe a series of older adult patients with postherpetic myofascial pain, a heretofore rarely described complication of herpes zoster. Design. Case series. Setting. Outpatient older adult pain clinic. Patients. Five older adults are presented with myofascial pain that developed as a complication of herpes zoster. Results. Pain duration at the time of presentation ranged from 4 months to 7 years. All patients reported functional impairment from pain despite oral analgesics. Myofascial pathology was diagnosed by the presence of taut bands and trigger points in the affected myotome. Upon successful treatment of the myofascial pain with nonpharmacologic modalities (e.g., physical therapy, trigger point injections, dry needling, and/or percutaneous electrical nerve stimulation), all patients reported symptomatic improvement, and four out of five were able to significantly reduce or discontinue their opioids. Conclusion. Postherpetic pain is traditionally conceptualized as a purely sensory phenomenon. Identification of the intrusion of a myofascial component may be worthwhile, both from the standpoint of enhanced pain relief and reduction in the need for oral analgesics. Formal exploration of this phenomenon is needed.

Allerg Immunol (Paris) 2006 Feb; 38(2): 62-4 (Read article online)

Galadari I, Fowzan AW

Fifty patients with oral ulcers were studied clinically and investigated for the detections of Herpes Simplex Virus (HSV) through virus isolation from their lesions (vesicles and ulcers) and detection of the presence of antiviral antibodies (both, IgM and IgG) in their sera using the indirect immunofluorescene (IIF) technique. The results of this study proved that virus isolation is the most reliable method for diagnosis, though the use of antibody serological tests could be a useful adjunct to virus isolation in situations where a rapid laboratory diagnosis is needed. Oral Herpes Simplex virus infection can be viewed, in the main, as a trivial disorder causing patients minor physical discomfort. The prevalence of HSV may be high in innocent infections, as high as 1/3 of the population. However, HSV infection and its complications with troublesome recurrences may make the problem worse. The apparent increase in HSV infection over recent years may be partly due to increased publicity about the disease, the current antiviral treatment, the inclusion of both primary and recurrent cases in clinic follow up and the increased use of viral cultures for diagnosis. The aim of this work is to share in the study of the detection of HSV through virus isolation and detection of antiviral antibodies using IIF technique, as well as the evaluation of the diagnosis by the above mentioned methods.

Scand J Infect Dis 2006; 38(4): 281-9 (Read article online)

Burton CM, Kristensen P, Lützhøft R, Rasmussen M, Milman N, Carlsen J, Christiansen CB, Andersen CB, Iversen M

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality in lung transplant recipients. We investigated the incidence of CMV infection in relation to CMV prophylaxis, and recipient-donor CMV serotype, in a cohort of 250 consecutive lung transplant recipients. All patients received 3 months CMV prophylaxis with acyclovir (n = 67) or gancyclovir (n = 183). Recipient-donor CMV serotype matching was performed in patients receiving acyclovir: R+/D+(n = 38), R+/D-(n = 10), R-/D+(n = 1), R- /D-(n = 16), unknown (n = 2). Recipient-donor CMV serotype matching was not performed in patients receiving gancyclovir: R+/D+(n = 71), R+/D-(n = 42), R-/D+(n = 38), R-/D-(n = 31), unknown (n = 1). The overall incidence of CMV infection was 51% (n = 34) in the acyclovir group, and 42% (n = 77) in the gancyclovir group (p = 0.14). During the first 9 months after transplantation, the rate of CMV infection was higher in the acyclovir group (42%) compared with the gancyclovir group (30%) (p = 0.005). Multivariate analysis demonstrated the incidence of CMV infection during the first 9 months was higher for acyclovir prophylaxis (p<0.001) and R-/D+ serostatus (p<0.001) and lower with R-/D- serostatus (p = 0.02). In conclusion, gancyclovir significantly delays the onset of first CMV infection among lung transplant patients. CMV surveillance and choice of prophylaxis may be modified according to donor-recipient CMV serotype.

Clin Neurol Neurosurg 2006 May 17; (Read article online)

Ginanneschi F, Donati D, Moschettini D, Dominici F, Cermelli C, Rossi A

An active co-infection with CMV and HHV-7 has been never described in immunocompetent patients. The authors describe a case of encephaloradiculomyelitis in an immunocompetent man. Polymerase chain reaction (PCR) performed on cerebrospinal fluid (CSF) showed positivity for DNA of Cytomegalovirus (CMV) and Herpes-virus type 7 (HHV-7), whereas the same test applied on peripheral blood mononuclear cells gave negative result. These results are highly supportive of an infection of the central and peripheral nervous systems, caused by CMV and HHV7. Such viral co-infection has only been described in immune-depressed patients with CMV disease, in which HHV-7 was supposed to act as a cofactor, enhancing clinical manifestations. The same mechanism is presumably responsible for the development of encephaloradiculomyelitis clinical signs in the present case. This is the second case in which DNA of HHV-7 has been found in the CSF of an adult immunocompetent patient. This novel observation suggests that the search for viral DNA in the CSF should be performed also in immunocompetent patients.

Eur Heart J 2006 May 22; (Read article online)

Levy PY, Fournier PE, Charrel R, Metras D, Habib G, Raoult D

AIMS: Aetiological investigations of pericardial effusion are often negative. We evaluate the interest of systematic analysis of fluid in order to diminish the number of pericarditis classified as idiopathic. METHODS AND RESULTS: We performed a systematic analysis of pericardial fluid and biopsy specimens, using cultures and molecular analyses for the identification of bacteriological, fungal, and viral agents, as well as histopathological examination of 106 pericardial fluid samples. The aetiological diagnosis was determined clinically and by non-invasive procedures in 40 and nine patients, respectively. In the remaining 57 patients, 14 neoplasias and 17 infections were diagnosed. Molecular procedures identified seven viral (Enterovirus, Herpes simplex virus, and Epstein-Barr virus in four, two, and one of the cases, respectively), one fungal (Cryptococcus neoformans), and nine bacterial infections. Four of these bacteria were not diagnosed by culture because of prior antibiotics treatment (Mycobacterium tuberculosis in two cases, Streptococcus pneumoniae in one case, and Actinomyces neuii in one case). The aetiology remained undetermined in 26 patients. CONCLUSION: The systematic use of molecular techniques permitted a significant increase in aetiological diagnoses of punctured pericardial effusions when compared with cultures (39.5 vs. 13.9%, respectively; P<0.01). It is particularly beneficial for patients with a previous antibiotic regimen or suspicion of tuberculosis.

Eur J Drug Metab Pharmacokinet 2006 Jan-Mar; 31(1): 17-20 (Read article online)

Yang Q, Hu Q

The pharmacokinetics and bioavailability of acyclovir sustained-release tablets in dogs were investigated. Blood concentrations of acyclovir were determined by RP-HPLC after a single oral dose of two kinds of acyclovir tablets given separately to 6 beagle dogs. The main pharmacokinetics parameters of the acyclovir sustained-release tablet were as follows: T1/2, Tmax and Cmax were 4.10 +/- 0.20 h, 4.05 +/- 0.54 h and 6.90 +/- 0.68 [microg x ml(-1), respectively. MRT was 9.02 +/- 0.44 h. Using acyclovir standard tablet as control, relative bioavailability of the acyclovir sustained-release tablet was 152.2 +/- 49.90%. According to the two-tailed t-test, there was a distinct difference in the data for Tmax, Cmax and AUC between acyclovir sustained-release tablets and acyclovir standard tablets, and the absorbability of acyclovir sustained-release tablets was much better than that of the acyclovir standard tablets.

Atherosclerosis 2006 May 16; (Read article online)

Marchesi S, Lupattelli G, Sensini A, Lombardini R, Brozzetti M, Roscini AR, Siepi D, Mannarino E, Vaudo G

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15mg/dL versus 0.07+/-0.08mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107ng/mL versus 325+/-80ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.

J Huazhong Univ Sci Technolog Med Sci 2006; 26(1): 145-7 (Read article online)

Deng Y, Yang D, Chen X, Chen Y

In order to investigate the IFN-gamma and IL-4 expression of CD8+ T lymphocytes in the peripheral blood from patients with recurrent genital herpes (RGH) at different clinical periods and their relationship with the pathogenesis of RGH, flow cytometry was used to detect the intracellular cytokines (IFN-gamma and IL-4) of CD8+ T lymphocytes in the peripheral blood of 30 patients with RGH at acute period, 20 patients with RGH at recovery period and 15 healthy volunteers. The results showed that RGH patients at acute period had a lower percentage of Tc1 subsets in peripheral blood than that of healthy controls (P < 0.001), especially a remarkable decreased percentage of Tc1 subsets (P < 0.001) among those RGH patients with recurrent number more than 3 in the recent half a year. Tc1/Tc2 ratio in the RGH patients at acute period was significantly decreased as compared with normal control group (P < 0.05). The recurrent number of acute patients in the recent half a year was significantly correlated with the percentage of Tc1 subsets and the ratio of Tc1/Tc2 (P < 0.05). A decreased percentage of Tc1 subsets was found among the RGH patients with recurrent number more than 3 in the recent half a year at recovery period in comparison with healthy volunteers (P < 0.05), and it was significantly correlated with the recurrent number in the recent half a year (P < 0.05). It is concluded that there are Tc1/Tc2 imbalance and a low level of Tc1 subsets in RGH patients who are relapsing repeatedly in the near period. The low level of Tc1 subsets may be an important factor for the recurrence of RGH and the reactivation of latent herpesvirus infection.

Hum Gene Ther 2006 May; 17(5): 518-530 (Read article online)

O'brien TA, Tuong DT, Basso LM, McIvor RS, Orchard PJ

Donor T lymphocytes genetically engineered to express a "suicide gene" to facilitate negative selection represent a promising strategy for the management of graft-versus-host disease occurring after allogeneic hematopoietic cell transplantation (HCT). For this purpose, the herpes simplex virus thymidine kinase (HSV-tk) gene, although well studied, has limitations. Cytosine deaminase (CD), an alternative gene for negative selection, converts 5-fluorocytosine (5-FC) to the toxic metabolite 5-fluorouracil (5-FU). Sensitivity of cells to 5-FU can be further increased by expression of uracil phosphoribosyltransferase (UPRT), which catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate. By using a chimeric gene (NG/CD) expressing the truncated human nerve growth factor receptor (NGFR) for positive selection fused to the Saccharomyces cerevisiae CD gene, we investigated strategies to achieve optimal T cell eradication by CD and UPRT expression, utilizing a single retroviral vector. Three vector strategies were compared on the basis of NGFR expression by flow cytometry, western analysis, and enzymatic activity. A construct (NG/CDiU) expressing UPRT and NG/CD, using a bicistronic message, provided the greatest UPRT activity and killing, reducing the lethal dose of 5-FC sufficient to eradicate 90% of cells from 38.7 mug/ml (300 muM) (NG/CD expression alone) to 0.13 mug/ml (1 muM). This approach provides an effective alternative to the HSV-tk system for eradication of donor T lymphocytes after allogeneic HCT.

Wien Klin Wochenschr 2006 Mar; 118(3-4): 90-94 (Read article online)

Kränke B, Trummer M, Brabek E, Komericki P, Turek TD, Aberer W

BACKGROUND: Perianal dermatitis is probably the most common cutaneous disorder of the genitoanal area. Studies on the epidemiology of causative factors are rare. METHODS: Over a 4-year period we prospectively studied 126 patients with a presumptive diagnosis of anal eczema. The diagnostic algorithm comprised medical history, inspection, microbiology, laboratory chemistry, patch tests, proctoscopy, and biopsy if appropriate. RESULTS: The age range was 7-82 years and the majority of patients were male (57.1%). Periods of anal symptomatology ranged from 6 days to 120 months and most of the patients (51.6%) had complaints for more than 12 months. The clinical diagnosis in 68 patients (54%) was: intertrigo/candidiasis (42.9%), atopic dermatitis (6.3%), pruritus ani (5.6%), psoriasis (3.2%), skin atrophy from steroid use (2.4%), lichen sclerosus et atrophicus (n = 2), herpes simplex (n = 1), and condylomata acuminata (n = 1). Contact eczema was suspected in 58 patients (46%), but 25 of these (43.1%) showed no contact sensitization. CONCLUSION: The majority of patients with symptoms of anal eczema suffer from intertrigo/candidiasis, and relevant, causative contact sensitization may be found in only some of them. Patch-testing is a valuable investigative tool only when the patients' own products are included in the test series. Most patients suffer from their perianal complaints for more than 12 months, therefore diligent evaluation is warranted.

Neurosurg Focus 2006; 20(4): e26 (Read article online)

Gupta V, Wang W, Sosnowski BA, Hofman FM, Chen TC

Object. Adenovirus transduction in gene therapy is dependent on the expression of the coxsackie virus-adenovirus receptor (CAR) for initial binding and on the integrin receptors (avb3, avb5) for viral internalization. Low and variable expression of CAR may be responsible for the low transduction rates seen with native adenoviral vectors. The goal of this study was to demonstrate increased transduction efficiency by retargeting the adenovirus with a fibroblast growth factor (FGF) ligand, FGF-2. Methods. The retargeted adenoviruses were used to transduce human glioblastoma multiforme (GBM)-derived ECs (tumor-associated brain endothelial cells [TuBECs]), in which there is minimal CAR expression but a high expression of FGF receptor (FGFR). The results demonstrate that the transduction efficiency of TuBECs can reach as high as 80% when one uses an FGF2-conjugated adenovirus containing green fluorescent protein (FGF2-AdGFP) yet be only 5% when one uses the native adenovirus (AdGFP). The TuBECs were transduced with either a native adenovirus (AdHSV-TK) or a retargeted adenovirus (FGF2-AdHSV-TK), both of which carry the suicide herpes simplex virus-thymidine kinase (HSV-TK) gene. Administered as a cytotoxic prodrug, ganciclovir induced a significant decline in the proliferation rate and increased apoptosis in TuBECs treated with the retargeted adenovirus, compared with its effect on TuBECs treated with the native adenovirus. Increased transduction efficiency was determined by performing GFP-based flow cytometry, and the expression of the TK protein by the retargeted adenovirus was assessed by performing an immunohistochemical analysis focused on HSV-TK. The mechanism of cytotoxicity was determined to be apoptosis by performing a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Conclusions. Fibroblast growth factor-2-retargeted adenoviral vectors may be used to increase the transduction of GBM-derived endothelial cells, enabling a new and efficient antiangiogenesis strategy for the treatment of malignant gliomas.

Drugs Today (Barc) 2006 Apr; 42(4): 249-54 (Read article online)

Caple J

Current strategies for managing herpes zoster show variable efficacy and do not prevent its appearance. Varicella-zoster virus vaccine, or "zoster vaccine" is a more potent form of the varicella-zoster virus vaccine currently approved for use in the prevention of varicella in children. Zoster vaccine decreases the incidence of herpes zoster and burden of illness in adults aged 60 years and older and appears more efficacious in patients aged 60-69 than in those over 70 years. Importantly, the incidence of postherpetic neuralgia is significantly reduced in patients who receive zoster vaccine, irrespective of age or sex. The duration of postherpetic neuralgia is also significantly reduced. Zoster vaccine has a favorable safety profile; most treatment-related adverse events are related to the site of injection. This review summarizes the current data on the clinical efficacy and safety of zoster vaccine in adults aged 60 years and older. (c) 2006 Prous Science. All rights reserved.

Oral Dis 2006 May; 12(3): 254-70 (Read article online)

Arduino PG, Porter SR

Herpes simplex virus type 1 (HSV-1) gives rise to a variety of clinical disorders and is a major cause of morbidity and mortality worldwide. HSV-1 infections are common in oral and perioral area. The aim of the present report was to critically examine the published literature to evaluate the advantages and limitations of therapy of HSV-1 infection in both immunocompetent and immunocompromised patients. Systemic antiviral therapy has been widely accepted as effective for primary herpetic gingivostomatitis. Aciclovir (ACV) 5% cream seems to be the accepted standard topical therapy for herpes labialis, being both effective and well tolerated, although penciclovir 1% cream has been proposed as a potentially useful treatment. Systemic ACV may be effective in reducing the duration of symptoms of recurrent HSV-1 infection, but the optimal timing and dose of the treatment are uncertain. Aciclovir and famciclovir may be of benefit in the acute treatment of severe HSV-1 disease in immunocompromised patients. There is also evidence that prophylactic oral ACV may reduce the frequency and severity of recurrent attack of herpetic infection in immunocompromised patients, but the optimal timing and duration of treatment is uncertain and can vary in different situations.

J Interferon Cytokine Res 2006 Apr; 26(4): 220-5 (Read article online)

Austin BA, Halford W, Silverman RH, Williams BR, Carr DJ

Three interferon-gamma (IFN-gamma)-induced antiviral pathways have been reported. Involved antiviral proteins include: Mx, RNase L/2',5'-OAS, and protein kinase R (PKR). Involvement of OAS and PKR in IFN-gamma-induced anti-herpes simplex virus-1 (HSV-1) pathways has not been reported previously, but IFN-gamma induces OAS and PKR when other viruses invade the nervous system. The aim of the current study was to determine if the absence of intact OAS and PKR antiviral pathways affects the antiviral activity of IFN-gamma during acute HSV-1 infection within the trigeminal ganglia (TG). To investigate this, primary TG cultures were established using TGs removed from C57BL/6 (wild-type), RNase L knockout, and RNase L/PKR double knockout mice. Each dissociated TG was transduced with an adenoviral vector containing an IFN-gamma transgene or vector alone. Viral titers after HSV-1 infection of primary TG cell cultures were determined. Significant differences in viral titer for Ad:Null-transduced vs. Ad:IFN-gamma-tranduced TG were found in each genotype. However, the effectiveness of Ad:IFN-gamma was not reduced in the absence of both OAS and PKR pathways or OAS alone. Recombinant IFN-gamma also exhibited anti-HSV-1 activity. The effectiveness of the IFN-gamma transgene was lost in primary TG cells from IFN-gamma receptor knockout mice. The data suggest that novel anti-HSV-1 mechanisms are induced by IFN-gamma.

J Intern Med 2006 Jun; 259(6): 615-8 (Read article online)

VAN DER Meer JW, Weemaes CM, VAN Krieken JH, Blomjous CE, VAN Die CE, Netea MG, Bredie SJ

The autosomal-dominant (AD) form of the hyperimmunoglobulin E syndrome (HIES) has been described as a multisystem disorder including immune, skeletal and dental abnormalities. Recently, the evaluation of patients from families in which HIES was inherited in a manner more consistent with autosomal-recessive (AR) inheritance, showed that AR-HIES is a clinically distinct disease entity. In addition to classical immunologic findings of AD-HIES, the AR form presents with severe recurrent fungal and viral infections with herpes zoster, herpes simplex and characteristic mollusca contagiosa. Furthermore, cerebral vascular sequelae, including vasculitis, infarction and haemorrhage were noted. In this report, we describe the clinical picture of two patients who showed remarkable resemblance to the description of AR-HIES, but also developed fatal aneurysmal dilatation of the thoracic aorta in adolescence. This finding may further consummate the clinical picture of AR-HIES and emphasize the possibility to develop early aortitis, most likely preceding the critical aneurysm formation at older age. This process should be anticipated during childhood in cases with AR-HIES.

Mol Cell Endocrinol 2006 May 14; (Read article online)

Steingart RA, Gozes I

Activity-dependent neuroprotective protein (ADNP) is essential for brain formation. Here, we investigated the potential neuroprotective effects of recombinant ADNP under stress conditions. The human ADNP cDNA was sub-cloned into a vector that contains VP22, a Herpes virus protein that may allow penetration of fused proteins through cellular membranes. When incubated with pheochromocytoma (PC12) cells, a neuronal model, VP22-ADNP was associated with the cells after a 25-min incubation period. Pre-incubation with VP22-ADNP enriched protein fractions protected against beta amyloid peptide toxicity and oxidative stress (H(2)O(2)) in PC12 cells. VP22 by itself was devoid of protective activity. Furthermore, the pro-apoptotic protein p53 increased by 3.5-fold from control levels in the presence of H(2)O(2), while treatment with VP22-ADNP prior to H(2)O(2) exposure significantly reduced the p53 protein levels. ADNP expression was previously shown to oscillate as a function of the estrus cycle in the mouse arcuate nucleus, these oscillations are now correlated with increased cellular protection.

Clin Cancer Res 2006 May 15; 12(10): 3152-7 (Read article online)

Fu X, Tao L, Li M, Fisher WE, Zhang X

PURPOSE: Pancreatic cancer is a devastating disease that is almost universally fatal because of the lack of effective treatments. We recently constructed a novel oncolytic virus (FusOn-H2) from the type 2 herpes simplex virus. Because the replication potential of FusOn-H2 depends on the activation of the Ras signaling pathway, we evaluated its antitumor effect against pancreatic cancer, which often harbors K-ras gene mutations. EXPERIMENTAL DESIGN: Human pancreatic cancer xenografts were established in nude mice either s.c. or orthotopically (n = 8/group). FusOn-H2 was injected either directly (s.c. tumors) or by the i.v. or i.p. route (orthotopic tumors). Tumor volume, weight, and survival time were recorded for each animal. Statistical analyses were done by Student's t test. RESULTS: A single intratumor injection of FusOn-H2 completely eradicated s.c. pancreatic cancers in all animals. Systemic injection of the oncolytic virus produced clear antitumor effects but did not abolish tumors in any animal. The most striking antitumor effect was seen when the virus was given i.p. Delivery of FusOn-H2 by this route completely eradicated established orthotopic tumors in 75% of the animals and completely prevented local metastases. CONCLUSIONS: FusOn-H2 has potent activity against human pancreatic cancer xenografts and may be a promising candidate for investigative virotherapy of this malignancy.

Aging Clin Exp Res 2006 Apr; 18(2): 171-3 (Read article online)

Pawelec G, Gouttefangeas C

Dysfunctional T-cell immunity contributes to susceptibility to infectious disease in the elderly. A characteristic feature of this "immunosenescence" is the predominance of clonal expansions of CD8 cells and decreased diversity of the T-cell antigen receptor repertoire. Lifelong chronic antigenic stress commonly caused by infection with persistent activating herpes viruses causes the accumulation of anergic, apoptosis-resistant CD8 T cells. These dysfunctional cells are indirectly immunosuppressive by tasking up the "immunological space" as well as directly suppressive via blockade of antigen presenting cells or cytokine secretion. They are associated with an emerging "immunological risk profile" predicting mortality in longitudinal studies of very old people. It is therefore hypothesized that for that majority of elderly people infected with cytomegalovirus (CMV), which seems to act as the dominant chronic stressor, anti-viral strategies would be of benefit in abrogating some of the detrimental clinical manifestations of immunosenescence.