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Myocarditis
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
PVB19 and HH6 have emerged as the main viruses causing myocarditis in the last few decades but, as most people are exposed to these viruses in life, their role as pathogenic in the myocardium is complex. PVB19, the causative agent of erythema infectiosum in infants and children, is considered responsible for hydrops fetalis and fetal death. The B19 receptor (erythrocyte P antigen) has been recognized on fetal myocardial cells suggesting that intrauterine myocarditis contributes to the development of fetal hydrops after PVB19 infection. About 80% of the general population have antibodies against B19. For the single-stranded DNA virus, B19V, the analysis of DNA copy number and VP1/VP2 RNA expression, representing transcriptional activity, are required as B19V DNA can also be found in the heart of healthy patients. HH6 virus is also acquired at an early age and most people are chronically infected. A systematic review shows PVB19V genomes in patients presenting with a clinical picture of myocarditis or DCM does not differ significantly from the findings in control myocardial tissues. Therefore, the aetiological role of PVB19V in the development of myocarditis and DCM still remains unclear, and PVB19V may be a bystander rather than a cause of myocarditis. Only high copy numbers of B19V DNA which are transcriptionally active are currently thought to be myocarditis-related. These problems with viral studies make treatment algorithms such as those in Fig. 6.11 not easy to apply internationally.
Gene therapy in uveitis
Published in A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha, Vitreoretinal Surgical Techniques, 2019
Lim Wee-Kiak, Nussenblatt Robert B
Adeno-associated virus (AAV) was originally identified as a contaminant in adenovirus preparations. AAV is a parvo-virus, a single-stranded DNA virus, which has so far showed no pathologic signs upon infection in humans for any of the six serotypes, each with a different cell specificity. AAV is a small virus with only two viral genes, rep and cap , which encode for replication and encapsulation. Deletion of these two genes allows therapeutic genes to be inserted.19–;21 For
Human Bocavirus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
José Luiz Proença-Módena, Guilherme Paier Milanez, Eurico Arruda
Classified within the single-stranded DNA virus genus Bocaparvovirus, human bocavirus consists of four subtypes (HBoV1-4) that are implicated in respiratory and gastrointestinal infections. Specifically, HBoV1 is associated with pediatric respiratory illness, but may be occasionally detected in patients showing gastrointestinal symptoms. HBoV2, HBoV3, and HBoV4 are largely present in stool samples of patients suffering from gastroenteritis. Given their co-occurrence with other viral and bacterial pathogens, there is much to be learned about the role of HBoV in the initiation of infection and pathogenesis. Since most HBoV studies lack an appropriate control group and do not employ methods that identify actively replicating viral particles, it is difficult to prove that the infection with the virus results in disease. The absence of robust experimental models is another obstacle in research with HBoV. Therefore, well-designed studies, with appropriate controls, and the development of techniques, including animal models, able to propagate and detect infectious HBoV virions, will be essential to advance our knowledge on the biology and pathogenesis of this parvovirus.
Oncolytic virus therapy for malignant gliomas: entering the new era
Published in Expert Opinion on Biological Therapy, 2023
Hirotaka Fudaba, Hiroaki Wakimoto
HSV-1 is an enveloped double-stranded liner-DNA virus of the Herpesviridae family. The HSV-1 genome is approximately 152 kb in size and encodes at least 80 open reading frames. Genetic modifications of the HSV-1 genome can eliminate toxicity to normal cells and enable the arming of various exogenous genes. Adenovirus is a non-enveloped double-stranded DNA virus of the Adenoviridae family. The well-established biology of human adenovirus type 5 leads to generating oncolytic adenovirus after genetic manipulation and modification. Vaccinia virus is an enveloped double-stranded DNA virus and belongs to the poxviridae family. H-1 parvovirus (H-1PV, ParvOryx) is a small, non-enveloped, single-stranded DNA virus of the parvoviridae family whose natural host is the rat. Humans are not naturally infected and therefore lack neutralizing antibodies [7].
Alpha-1 antitrypsin deficiency: current therapy and emerging targets
Published in Expert Review of Respiratory Medicine, 2023
Oisín F. McElvaney, Daniel D. Fraughen, Oliver J. McElvaney, Tomás P. Carroll, Noel G. McElvaney
As AATD is a monogenic disorder, gene therapy would seem to provide a potential therapeutic option. The most commonly employed gene-delivery vector to date is the adeno associated virus (AAV), a single stranded DNA virus which can infect a variety of cells with low immunogenicity and stable long term expression. In the first human study in AATD, an AAV vector containing the AAT cDNA was administered intramuscularly. The level of AAT achieved was well below the putative protective threshold (PPT). Patients developed neutralizing antibodies against the AAV capsid but the expression lasted for up to one year [72]. A subsequent trial using a herpes-simplex virus-1 helper system showed a 10-fold higher level compared to the first trial but AAT levels remained below the PPT. This study required multiple intramuscular injections. Subsequent evaluation showed sustained AAT transgene expression of around 3% of the PPT with other downstream effects consistent with an increased antiprotease screen in blood [73].
Gene therapy for neurological disorders: challenges and recent advancements
Published in Journal of Drug Targeting, 2020
Stefanie A. Pena, Rahul Iyengar, Rebecca S. Eshraghi, Nicole Bencie, Jeenu Mittal, Abdulrahman Aljohani, Rahul Mittal, Adrien A. Eshraghi
Adeno-associated virus (AAV) is an enveloped single-stranded DNA virus (Figure 7) that is currently the most frequently used viral vector due to its many favourable characteristics. AAV cannot replicate on its own and is non-pathogenic, rendering it unable to cause large adverse immune reactions or superinfections [75]. The virus can be engineered to contain nearly no viral genetic material, yielding targeted transcription of the intended gene with no generation of viral proteins [76]. Once the genetic material has been delivered, AAV remains episomal or extra-chromosomal, meaning it does not integrate into the host genome. This feature prevents unintended insertional mutagenesis following gene delivery [77]. However, AAV still exhibits years of long-term gene expression in the human brain [78]. Several different AAV serotypes, or coating proteins, allow for precise cell targeting and spreading in the CNS [79]. Variable capsid designs confer different tissue tropisms and distribution allowing AAV, for instance, to replace survival motor neuron protein (SMN) in treating spinal muscular atrophy (SMA) [13,80], silence superoxide dismutase-1 (SOD1) to treat ALS [81,82], or silence Huntington (HTT) to treat Huntington’s disease [81]. The major limitation of AAV is its extremely small size, which allows for excellent tissue spread but limits the size of therapeutic genetic material to less than 5 kB [83,84].