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Herpesvirus microRNAs for Use in Gene Therapy Immune-Evasion Strategies
Published in Yashwant Pathak, Gene Delivery, 2022
Vineet Mahajan, Shruti Saptarshi, Yashwant Pathak
The human cytomegalovirus (HCMV) is a beta herpes virus with a 230 kbp double stranded DNA, implicated in congenital infections that can be transmitted across the placental barrier, infected body fluids, and organ transplantation.29 HCMV infect a broad range of cell types via varied mechanisms. Among all Herpesviridae, HCMV has the largest genome. HCMV infection in the immunocompromised and individuals undergoing immunosuppressive treatments can be life threatening.
Order Ortervirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Kirchmeier et al. (2014) constructed a prophylactic vaccine to prevent the congenital transmission of human cytomegalovirus (HCMV). Thus, the MLV VLPs were used to express either full-length CMV protein gB or the full extracellular domain of CMV gB fused with the transmembrane and cytoplasmic domains from VSV protein G. Schädler et al. (2019) were the first to use the MLV VLPs as a scaffold for the vaccine against infectious laryngotracheitis virus (ILTV), a herpesvirus and member of the Gallid alphaherpesvirus 1 species. Recently, the MLV platform was employed to produce VLPs pseudotyped with the short (ΔS) version of the spike protein S from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; Roy et al. 2021).
Determination of Antiviral Activity
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Cytomegalovirus animal models are summarized in Table 5. The human cytomegalovirus is not known to be infectious to laboratory animals, so animal studies have been limited to nonhuman strains. The murine cytomegalovirus is quite infectious for mice, with intraperitoneal injection of large doses causing death of the animal [77]. Inoculation of lower doses will produce a more chronic infection that appears similar to that seen in the human. This chronicity has been seen in mice, guinea pigs, rats, and hamsters, manifested primarly through demonstration of inclusion bodies in submaxillary glands and recovery of virus from various tissues of the animals. The murine virus infection of pregnant mice causes a significant reduction in number of viable offspring; such a model may be useful in determining the value of an antiviral substance on negating such pregnancy wastage. Little work has been reported on the usefulness of the other models listed. One may wish to consider, as an ultimate antiviral test, the usefulness of a cytomegalovirus-inhibitory substance in an immunosuppressed animal, since the cytomegalic diseases in similarly stressed humans are so extensive.
Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections
Published in Expert Opinion on Therapeutic Targets, 2022
Christopher Schwake, Michael Hyon, Athar H. Chishti
Human cytomegalovirus is transmitted mainly through organ transplant recipients and congenital infections. HCMV can establish infection by hijacking the host SPP processing of signal peptides from the MHC class I molecules such as HLA-A which then complex with HLA-E [72]. Once at the cell surface, the HLA-E complex binds to CD94 on natural killer cells to prevent lysis [73]. Through this process, MHC class I-expressing cells are protected from NK killing. During HCMV infection, the virus expresses UL40 containing a signal sequence identical to that of HLA-E [74,75]. After cleavage by signal peptidase, further processing of UL40 by SPP creates an identical ligand for host HLA-E. Once presented on the cell surface of the virally infected cell, the subsequent NK-mediated lysis is thwarted (Figure 5C) [76]. HCMV encodes other proteins to evade the immune system. One such immunoevasin, US2, associates with SPP resulting in the removal of MHC class I peptides from the cellular surface [77]. The consequence of SPP-mediated US2 processing leads to reduced immune recognition and infected cell clearance. The precise mechanism for how US2 performs this function is not known. It is possible that SPP is involved in the ERAD of MHC I molecules and that US2 shuttles MHC I molecules to the SPP complex. Further studies will be needed to elucidate the mechanistic underpinnings of the US2/SPP complex in immune evasion.
Role of environmental factors in multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2021
Amin Zarghami, Ying Li, Suzi B. Claflin, Ingrid van der Mei, Bruce V. Taylor
Human cytomegalovirus (CMV) is another member of the herpesvirus family with a wide range of clinical manifestations, ranging from asymptomatic in most healthy individuals to severe infections in immunocompromised individuals [147]. A 2020 meta-analysis (n = 15) reported a non-significant difference in CMV (IgG) seroprevalence between 3591 adult PwMS and 4241 controls (OR:1.19; 95%CI:0.78–1.81). Due to the heterogeneity (I2 = 33%) observed between studies, a subgroup analysis based on geographic region was conducted. This analysis showed that MS cases were less likely to be CMV IgG positive compared to controls (OR:0.75; 95%CI: 0.60–0.94) in European countries, whereas in the Middle East, living with MS was associated with an increased likelihood of CMV IgG seropositivity (OR:5.09; 95%CI:1.07–24.26). No association was found among cases in North America [148]. In a 2014 meta-analysis based on data from 11 retrospective studies, CMV seropositivity was found to be protective against MS onset (OR:0.77; 95%CI: 0.67–0.87) when adjusted for risk factors associated with CMV and MS status [149]. A 2019 prospective nested case–control study (n = 116) did not find a significant association between maternal CMV IgG levels and risk of MS onset in offspring [116]. Studies evaluating the interaction between CMV and HLA genes on MS onset risk have been inconclusive [109,139,149].
Optimization of Ganciclovir use in allogeneic hematopoietic cell transplant recipients – the role of therapeutic drug monitoring
Published in Expert Review of Anti-infective Therapy, 2021
Su Ann Ho, Monica Slavin, Jason A. Roberts, Michelle Yong
Human cytomegalovirus (CMV) infection is ubiquitous globally with adult seroprevalence ranging from 45% to 100% in developed and developing countries, respectively, [1,2]. Following primary infection, complex host immune response interplay controls and directs the virus into latency [1]. This immune control is disrupted in allogeneic hematopoietic stem cell transplantation (HCT), enabling the development of active infection which can range from asymptomatic viremia to tissue-invasive CMV disease caused by the direct cytotoxic effects of the virus [3]. Approximately 70% of CMV seropositive recipients will experience early CMV reactivation (within the first 100 days post-transplant) [4]. The antiviral drug ganciclovir (and orally administered pro-drug, valganciclovir) has been the cornerstone for the management of CMV prophylaxis, infection, and disease.