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This study evaluated the effects of 12-hour transportation on immune responses to equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4). Possible replication of EHV-1 and EHV-4 was monitored by real-time PCR of nasal swabs and peripheral blood mononuclear cells (PBMCs), and changes in systemic and mucosal antibodies were investigated. Six healthy Thoroughbreds with transport experience were transported in commercial trucks, repeating the same three-hour route four times. Blood samples for cortisol measurement were taken before departure and every three hours. Nasal swabs, PBMCs, nasal wash and serum samples were collected before departure, at unloading, two and six days after arrival. Cortisol concentration increased significantly after three and six hours of transport (P < 0.05), confirming acute transport stress. However, no evidence of viral replication or lytic infection was observed, and serum virus neutralization (VN) titers for EHV-1 and EHV-4 were unchanged, except for one horse that showed a four-fold decrease in titer against EHV-1 after transportation. Urea and total IgA concentration in nasal washes increased significantly after transportation (P < 0.05), while total IgA/protein ratio was unchanged. A transient, ≥4-fold decrease in VN titers for EHV-1 in nasal wash concentrates was observed in four out of six horses after transportation (geometric mean titer declined from 202 to 57, P < 0.05), suggesting suppression of VN capacity in the nasal mucosa may contribute to susceptibility to EHV-1 after transportation. VN antibodies against EHV-4 in nasal secretion were not detected at any timepoint.

Background HHV-8/Kaposi Sarcoma herpesvirus has been associated with a broad spectrum of diseases in solid organ transplant (SOT) recipients. Primary donor-derived infection can be associated with severe and rapidly fatal non-neoplastic disease, and diagnosis is made with high HHV-8 DNAemia. Methods We carried out an international survey to investigate the current approach to HHV-8 screening, and management in SOT since a protocol has not been established by international guidelines. Results A total of 51 transplant centers from 15 countries filled out the survey. HHV-8-associated diseases in SOT have been diagnosed during the previous 5 years in 67% of centers. Pretransplant serological screening is performed in 17 centers (33%), and posttransplant HHV-8 nucleic acid testing (NAT) monitoring is performed in 21 centers (41%). Performing HHV-8 NAT monitoring and serological screening were found associated with having diagnosed in the previous 5 years a non-malignant HHV-8-associated disease. Conclusions Serological pretransplant screening of donors and recipients and post-transplant HHV-8 NAT monitoring recommendations should be standardized. Even though serological assays are not optimal, they could contribute to increasing knowledge on epidemiology and management of HHV-8-associated diseases after SOT.

Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which accelerates BoHV-1-induced apoptosis and increases virus replication. Herein, to elucidate the mechanism through TCDD modifies BoHV-1 infection, we analyzed the modulation of a members of Sirtuin proteins family in MDBK cells. We found that mitochondrial SIRT3 was upregulated during infection. This change was accompanied by cytoskeletal rearrangements and cell extensions. All these trends were drastically modified by TCDD. We hypothesize that, taken together, these results might further clarify the processes responsible for the action of TCDD on the BoHV-1 replication, resulting in enhanced virus production.

Human papillomaviruses (HPVs) are necessary, but not sufficient, for the development of cervical cancer (CC). Human β-herpesviruses (β-HHVs) have been suggested as possible cofactors in the oncogenesis of CC. In this cross-sectional study, the prevalence and possible association of cytomegalovirus (CMV), HHV-6 and -7 with HPV presence was investigated by quantitative real-time PCR assays in cervical samples obtained from 208 italian women. The two most common high-risk HPV types found were 31 and 16. Overall, the positive rates for CMV, HHV-6 and HHV-7 were 66%, 25%, and 6%, respectively. In particular, the prevalence of CMV was found to be extremely high irrespective of either the cytological category or HPV positivity. The prevalence of HHV-6 DNA was significantly higher in high-grade squamous intraepithelial lesions (HSIL) respect to normal women (P

We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

We describe an immunocompetent 61-year-old woman who was negative for human immunodeficiency virus and who had recurrent human herpesvirus 8 (HHV-8) infection associated with a relapsing systemic inflammatory syndrome characterized by fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, and rash. Kaposi's sarcoma developed 10 months after the initial clinical presentation. A correlation was documented between the recurrent clinical manifestations and the HHV-8 load in plasma and peripheral-blood mononuclear cells. Histologic examination of an enlarged lymph node heavily infected with HHV-8 revealed an atypical lymphoproliferative disorder characterized by paracortical hyperplasia and collapsed primary and secondary follicles.

Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease, associated with the reactivation of the human herpesvirus 6 (HHV-6) and/or human herpesvirus 7 (HHV-7) that usually lasts 6-8 weeks. We studied, from a clinical and virological point of view, 12 patients in whom the features of PR lasted longer than 12 weeks, defining this form of the disease as persistent PR (PPR). As in typical PR, in most of the PPR patients the disease begins with a herald patch, but compared to typical PR, systemic symptoms and oral lesions are more common. Moreover, in PPR we found a persistent reactivation of HHV-6 and/or HHV-7 with higher viral loads than in typical PR, accounting for the unusual persistence of the illness, the more frequent and severer systemic symptoms and the oral lesions. In conclusion, we describe an unusual persistent form of PR, whose prevalence has probably been underestimated so far and which should be added to the other variants of PR.

The study was performed to determine if there is an association between the genotype and transmission of HHV-8 types A and C. These HHV-8 subtypes are prevalent in the area of North of Sardinia, which is an island off west Italy's mainland that has a high HHV-8 seroprevalence (35%). Blood and saliva samples from 30 patients with classic Kaposi's sarcoma who were lifetime residents of North Sardinia were analyzed to identify the HHV-8 genotype and quantitate the viral load. Genotype A, especially A1 subtype, was found more frequently (9/30 patients) and had a significantly higher viral load in saliva compared to blood (P = 0.029), where type C was found more frequently but with a viral load lower than 103 copies/ml. To determine if there is a correlation between the viral genotype and cellular tropism, type A1 and C3 HHV-8 viral particles were obtained from cell lines BCBL1 and BC3 infected chronically with HHV-8 A1 and C3 genotypes respectively and used to infect HEK293 epithelial origin cells and PBMCs in vitro. The data indicate that the A1 HHV-8 genotype is tropic and replicates at higher levels in the epithelial cell lines. J. Med. Virol. 84:786–791, 2012. © 2012 Wiley Periodicals, Inc.

Specific herpesvirus-like DNA sequences have been found in Kaposi's sarcoma (KS) lesions of AIDS patients, suggesting that a novel gamma herpesvirus, homologous to Epstein-Barr virus and herpesvirus saimiri, could be implicated in the pathogenesis of KS. To better understand the role of this putative etiological agent, named Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8), we investigated by the polymerase chain reaction (PCR) the presence of viral DNA sequences in various organs obtained at autopsy from seven AIDS patients with KS and six without KS. For each sample, to exclude positive results due to visceral KS dissemination, the presence of microscopic foci of KS cells was rules out by histology and CD34 immunohistochemistry on serial frozen sections immediately adjacent to those employed for DNA extraction. PCR and nested PCR were performed with primers specific for the HIV-8 330 Bam fragment originally described by Chang et al. (Science 1994;266:1865-1869). As quality control, the extracted DNA was amplified with primers for human beta-globin. All KS legions were HHV-8 positive. In addition, extralesional KSHV DNA sequences were detected in seven of seven lymphoid organs and in five of five prostate glands of KS patients. Normal skin was positive in three of five cases and bone marrow in two of three tested cases, all other tissues being negative by PCR and nested PCR. By contrast, no virus was detected in tissue samples of AIDS cases without KS. The restricted organ distribution here documented argues for a selective tissue tropism of HHV-8 in vivo in AIDS patients and suggests that in the infected host lymphoid organs and the prostate gland may represent privileged sites of viral latency and persistence.

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

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 infection.