Induction of latent human cytomegalovirus by conventional gamma irradiation and prevention by treatment with INACTINE PEN110

Öhagen, Åsa; Gibaja, Veronica; Horrigan, Jeff; Lunderville, Douglas; Vasudevacharya, Jayarama; Marcello, Jennifer; Chapman, John; Lazo, Aris

doi:10.1111/j.1423-0410.2004.00532.x

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…[12,24,1,35] Researchers have shown that ionizing radiation is a risk factor for gliomas and that latent HCMV infection can be reactivated by exposure to radiation. [26] In our laboratory, we found that lymphocytes infected with HCMV exhibit chromosomal instability at levels equal to or above that seen in lymphocytes subjected to gamma irradiation. In addition, we have observed that HCMV increases the sensitivity of lymphocytes to the effects of radiation, leading to greater instability than that in lymphocytes treated with either HCMV or radiation individually.…”

Section: Discussionmentioning

confidence: 93%

Detection of human cytomegalovirus in different histological types of gliomas

et al. 2008

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The association between human cytomegalovirus (HCMV) infection and glioblastoma has been a source of debate in recent years because of conflicting laboratory reports concerning the presence of the virus in glioma tissue. HCMV is a ubiquitous herpesvirus that exhibits tropism for glial cells and has been shown to transform cells in vitro. Using sensitive immunohistochemical and in situ hybridization methods in 50 glioma samples, we detected HCMV antigen and DNA in 21/21 cases of glioblastoma, 9/12 cases of anaplastic gliomas, and 14/17 cases of low-grade gliomas. Reactivity against the HCMV IE1 antigen (72 kDa) exhibited histology-specific patterns with more nuclear staining for anaplastic and low-grade gliomas, while GBMs showed nuclear and cytoplasmic staining that likely occurs with latent infection. Using IHC, the number of HCMVpositive cells in GBMs was 79% compared to 48% in lower grade tumors. Non-tumor areas of the tissue contained only 4 % and 1% of HCMV-positive cells for GBMs and lower grade tumors, respectively. Hybridization to HCMV DNA in infected cells corresponded to patterns of immunoreactivity. Our findings support previous reports of the presence of HCMV infection in glioma tissues and advocate optimization of laboratory methods for the detection of active HCMV infections. This will allow for detection of low-level latent infections that may play an important role in the initiation and/or promotion of malignant gliomas.

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Section: Discussionmentioning

confidence: 93%

Detection of human cytomegalovirus in different histological types of gliomas

et al. 2008

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“…12,16,31 In 1 study, g-irradiated blood of unknown CMV status was used, 25 although this method does not inactivate CMV and may even increase CMV replication in latently infected cells. 32 Three studies did not mention any attempt to prevent or identify CMV transmission through transfused blood products. [13][14][15] In 2 studies, infants were prophylactically treated with intravenous Ig.…”

Section: Systematic Reviewmentioning

confidence: 99%

Breast Milk–Acquired Cytomegalovirus Infection and Disease in VLBW and Premature Infants

et al. 2013

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BACKGROUND: Very low birth weight (VLBW) and premature infants are at risk for developing postnatal cytomegalovirus (CMV) disease, including CMV-related sepsis-like syndrome (CMV-SLS) for which in the United States are lacking. METHODS: We performed a systematic review and meta-analysis to estimate the pooled proportions (and 95% confidence intervals) of VLBW and premature infants born to CMV-seropositive women with breast milk–acquired CMV infection and CMV-SLS. We combined these proportions with population-based rates of CMV seropositivity, breast milk feeding, VLBW, and prematurity to estimate annual rates of breast milk–acquired CMV infection and CMV-SLS in the United States. RESULTS: In our meta-analysis, among 299 infants fed untreated breast milk, we estimated 19% (11%–32%) acquired CMV infection and 4% (2%–7%) developed CMV-SLS. Assuming these proportions, we estimated a rate of breast milk–acquired CMV infection among VLBW and premature infants in the United States of 6.5% (3.7%–10.9%) and 1.4% (0.7%–2.4%) of CMV-SLS, corresponding to 600 infants with CMV-SLS in 2008. Among 212 infants fed frozen breast milk, our meta-analysis proportions were 13% (7%–24%) for infection and 5% (2%–12%) for CMV-SLS, yielding slightly lower rates of breast milk–acquired CMV infection (4.4%; 2.4%–8.2%) but similar rates of CMV-SLS (1.7%; 0.7%–4.1%). CONCLUSIONS: Breast milk–acquired CMV infection presenting with CMV-SLS is relatively rare. Prospective studies to better define the burden of disease are needed to refine guidelines for feeding breast milk from CMV-seropositive mothers to VLBW and premature infants.

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“…To regularly produce an attenuated live vaccine against babesiosis and in order to minimize the risk of viruses being introduced into an animal or animal population directly by the vaccination procedure, it would be advisable to use gamma irradiation of the substrate. However, it is important to recall that some viruses may become activated, such as that reported for human cytomegalovirus (HCV) after gamma irradiation 28 . Another study describes the difficulty for using radiation on HIV sterilization, and concluded that gamma irradiation should be disregarded as a significant virus inactivation method for bone allograft, as the irradiation dose required to achieve a sterility assurance level is 89 kGy, which exceeds current recommendations 29 …”

Section: Discussionmentioning

confidence: 99%

Bovine Babesiosis Live Vaccine Production

Rojas

Millán

Alvarado

et al. 2006

Annals of the New York Academy of Sciences

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Gamma irradiation on bovine serum and red blood cells (RBC) allows proliferation and growth of in vitro-cultured Babesia sp., and has potential application to inactivate contaminating viruses and bacteria from the substrate. Gamma irradiation with 25 kGy in a source of (60)Co was able to inactivate infectious bovine rinotracheitis (IBR) and bovine viral diarrhea (BVD) viruses in artificially contaminated serum; besides, bacteria were also eliminated. In vitro culture of Babesia bovis (B. bovis) in modified substrate, by adding irradiated serum with (60)Co at 25 kGy was propagated from 24-well culture plates to 225 cm(2) tissue culture flasks, and percentages of parasitized erythrocytes (PPE) from 2.4% to 8.8% were obtained. Infected RBC adapted to Irrad S were transferred to the irradiated substrate in vitro culture system, by using serum irradiated at 25 kGy and RBC from 10 to 70 Gy. The PPE ranged from 3.1 to 11. Culture of Babesia bigemina (B. bigemina) was established with Irrad S (25 kGy); its propagation was achieved in tissue culture flasks reaching PPE from 0.5 to 4.3 with no statistical difference (P > 0.05) when compared to the nonirradiated control culture (1.2-4.8). B. bigemina-infected RBCs were transferred to the modified culture system by adding irradiated serum and RBC (25 kGy and 70 Gy, respectively). PPE obtained in culture flasks were from 0.8 to 4.2. The results indicate that gamma irradiation is a suitable method to inactivate potential viral contamination and eliminate bacteria from bovine serum, to produce a live attenuated vaccine through the in vitro culture.

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Induction of latent human cytomegalovirus by conventional gamma irradiation and prevention by treatment with INACTINE PEN110

Abstract: These results demonstrate that gamma irradiation, at levels currently used to treat RCC, has the capacity to induce expression of CMV, whereas PEN110 inhibits CMV replication and efficiently inactivates the infected cells.

Cited by 14 publications

References 28 publications

Detection of human cytomegalovirus in different histological types of gliomas

Detection of human cytomegalovirus in different histological types of gliomas

Breast Milk–Acquired Cytomegalovirus Infection and Disease in VLBW and Premature Infants

Bovine Babesiosis Live Vaccine Production

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