Persistence of Human Herpesvirus 7 in Normal Tissues Detected by Expression of a Structural Antigen

Human herpesvirus 7 (HHV-7) infection in histologically normal human tissues was investigated by immunohistochemical detection of the 85-kDa tegument phosphoprotein (pp85) encoded by the U14 gene. So far, two cell types were recognized as sites of HHV-7 infection in vivo: CD4+ T lymphocytes, believed to be the site of latent infection, and epithelial cells of salivary glands, the site of productive infection and viral shedding. Unexpectedly, cells expressing the HHV-7 structural antigen were detectable in lungs, skin, and mammary glands. Morphologically and phenotypically, they were distinct from lymphocytes. Liver, kidney, and tonsils were positive, although the number of HHV-7-positive cells was low. Large intestine, spleen, and brain were negative. Different from the current notion of the state of HHV-7 in humans, the results show that a variety of tissues harbor cells at a late stage of infection and suggest that HHV-7 causes a persistent rather than a true latent infectio

Persistence of human herpesvirus 7 in normal tissues detected by expression of a structural antigen

Human herpesvirus 7 (HHV-7) infection in histologically normal human tissues was investigated by immunohistochemical detection of the 85-kDa tegument phosphoprotein (pp85) encoded by the U14 gene. So far, two cell types were recognized as sites of HHV-7 infection in vivo: CD4+ T lymphocytes, believed to be the site of latent infection, and epithelial cells of salivary glands, the site of productive infection and viral shedding. Unexpectedly, cells expressing the HHV-7 structural antigen were detectable in lungs, skin, and mammary glands. Morphologically and phenotypically, they were distinct from lymphocytes. Liver, kidney, and tonsils were positive, although the number of HHV-7-positive cells was low. Large intestine, spleen, and brain were negative. Different from the current notion of the state of HHV-7 in humans, the results show that a variety of tissues harbor cells at a late stage of infection and suggest that HHV-7 causes a persistent rather than a true latent infectio

Systemic delivery of HER2-retargeted oncolytic-HSV by mesenchymal stromal cells protects from lung and brain metastases

Fully retargeted oncolytic herpes simplex viruses (o-HSVs) gain cancer-specificity from redirection of tropism to cancer-specific receptors, and are non-attenuated. To overcome the hurdles of systemic delivery, and enable oncolytic viruses (o-viruses) to reach metastatic sites, carrier cells are being exploited. Mesenchymal stromal cells (MSCs) were never tested as carriers of retargeted o-viruses, given their scarse-null expression of the cancer-specific receptors. We report that MSCs from different sources can be forcedly infected with a HER2-retargeted oncolytic HSV. Progeny virus spread from MSCs to cancer cells in vitro and in vivo. We evaluated the organ distribution and therapeutic efficacy in two murine models of metastatic cancers, following a single i.v. injection of infected MSCs. As expected, the highest concentration of carrier-cells and of viral genomes was in the lungs. Viral genomes persisted throughout the body for at least two days. The growth of ovarian cancer lung metastases in nude mice was strongly inhibited, and the majority of treated mice appeared metastasis-free. The treatment significantly inhibited also breast cancer metastases to the brain in NSG mice, and reduced by more than one-half the metastatic burden in the brain

Human herpesvirus 6 (HHV-6) U94/REP protein inhibits betaherpesvirus replication.

Human herpesvirus 6 (HHV-6) is the only human herpesvirus encoding U94/rep, homologue to the parvovirus non-structural gene rep68/78. Results to date suggest that HHV-6 U94/rep might regulate viral gene expression and have a role in viral latency. To determine the effect of U94/REP upon viral replication, the protein was produced. The purified U94/REP retained the characteristic immunological features. It was internalized and localized in the nucleus of human cells, showing marked inhibitory activity on the replication of HHV-6 (both variants A and B). The effect of U94/REP was dose-dependent and sensitive to treatment with single-stranded but not double-stranded DNA. U94/REP inhibited the replication of other betaherpesviruses, HHV-7 and human cytomegalovirus, but had no effect on herpes simplex virus. These results confirm the action of U94/rep latency gene in the regulation of HHV-6 replication with implications for co-reactivations and latency of human betaherpesviruses

IPOD Study: Management of Acute Left Colonic Diverticulitis in Italian Surgical Departments

BACKGROUND: In recent years, the emergency management of acute left colonic diverticulitis (ALCD) has evolved dramatically despite lack of strong evidence. As a consequence, management strategies are frequently guided by surgeon's personal preference, rather than by scientific evidence. The primary aim of IPOD study (Italian Prospective Observational Diverticulitis study) is to describe both the diagnostic and treatment profiles of patients with ALCD in the Italian surgical departments. METHODS: IPOD study is a prospective observational study performed during a 6-month period (from April 1 2015 to September 1 2015) and including 89 Italian surgical departments. All consecutive patients with suspected clinical diagnosis of ALCD confirmed by imaging and seen by a surgeon were included in the study. The study was promoted by the Italian Society of Hospital Surgeons and the World Society of Emergency Surgery Italian chapter. RESULTS: Eleven hundred and twenty-five patients with a median age of 62 years [interquartile range (IQR), 51-74] were enrolled in the IPOD study. One thousand and fifty-four (93.7%) patients were hospitalized with a median duration of hospitalization of 7 days (IQR 5-10). Eight hundred and twenty-eight patients (73.6%) underwent medical treatment alone, 13 patients had percutaneous drainage (1.2%), and the other 284 (25.2%) patients underwent surgery as first treatment. Among 121 patients having diffuse peritonitis, 71 (58.7%) underwent Hartmann's resection. However, the Hartmann's resection was used even in patients with lower stages of ALCD (36/479; 7.5%) where other treatment options could be more adequate. CONCLUSIONS: The IPOD study demonstrates that in the Italian surgical departments treatment strategies for ALCD are often guided by the surgeon's personal preference

IPOD Study: Management of Acute Left Colonic Diverticulitis in Italian Surgical Departments.

Background: In recent years, the emergency management of acute left colonic diverticulitis (ALCD) has evolved dramatically despite lack of strong evidence. As a consequence, management strategies are frequently guided by surgeon’s personal preference, rather than by scientific evidence. The primary aim of IPOD study (Italian Prospective Observational Diverticulitis study) is to describe both the diagnostic and treatment profiles of patients with ALCD in the Italian surgical departments. Methods: IPOD study is a prospective observational study performed during a 6-month period (from April 1 2015 to September 1 2015) and including 89 Italian surgical departments. All consecutive patients with suspected clinical diagnosis of ALCD confirmed by imaging and seen by a surgeon were included in the study. The study was promoted by the Italian Society of Hospital Surgeons and the World Society of Emergency Surgery Italian chapter. Results: Eleven hundred and twenty-five patients with a median age of 62 years [interquartile range (IQR), 51–74] were enrolled in the IPOD study. One thousand and fifty-four (93.7%) patients were hospitalized with a median duration of hospitalization of 7 days (IQR 5–10). Eight hundred and twenty-eight patients (73.6%) underwent medical treatment alone, 13 patients had percutaneous drainage (1.2%), and the other 284 (25.2%) patients underwent surgery as first treatment. Among 121 patients having diffuse peritonitis, 71 (58.7%) underwent Hartmann’s resection. However, the Hartmann’s resection was used even in patients with lower stages of ALCD (36/479; 7.5%) where other treatment options could be more adequate. Conclusions: The IPOD study demonstrates that in the Italian surgical departments treatment strategies for ALCD are often guided by the surgeon’s personal preference