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HIV/AIDS
Published in Patricia G. Melloy, Viruses and Society, 2023
Researchers have tried two main approaches to finding an animal model for studying HIV/AIDS. First, scientists have made rodents (more commonly mice than rats) with a “humanized” immune system, in a challenging and time-sensitive process in which the mouse’s immune system is destroyed before maturing and replaced with cells and tissues of the human immune system, which can fully develop in the animal. Mice are a popular choice when a mammalian model is needed for biomedical research given that they are small, easy to maintain in a research facility, and have large litter sizes (Hatziioannou and Evans 2012; Agarwal et al. 2020; Dash et al. 2021). Although other animals, like cats, are known to be susceptible to a similar virus known as feline immunodeficiency virus (FIV), there are major limitations to this model, including the types of cells infected by FIV versus HIV as well as the course of the illness potentially being longer with FIV versus HIV (Hatziioannou and Evans 2012). In the second approach, nonhuman primates are studied using simian immunodeficiency virus (SIV) or a modified version of SIV that looks like HIV called SHIV. Four different species of Asian macaques are used commonly (Hatziioannou and Evans 2012). However, some researchers have noted that vaccine trials first tested in nonhuman primates and then brought to human clinical trials have failed, indicating that a better animal model approach is needed. Advances in the sophistication of the humanized mouse models may become the go-to animal model in the future (Agarwal et al. 2020).
The Immunological System and Neoplasia
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Feline leukemia is a complex disease caused by a horizontally transmitted exogenous retrovirus. One of the common consequences of infection with feline leukemia virus (FeLV) is immunosuppression due mostly to lymphopenia as a result of a reduction in T lymphocytes. The immunosuppression was originally linked to survival of tumor cells rather than to a disease entity in its own right. The discovery of a human immunodeficiency virus (HIV), a retrovirus, as the etiological agent of the acquired immunodeficiency syndrome (AIDS) and the subsequent finding of additional retroviruses linked to immunodeficiencies in other mammalian species including cats stimulated reexamination of retroviral diseases in animals. The isolation of a feline immunodeficiency virus (FTV) was important because it not only provided a model for AIDS research, but because it complicated the clinical picture of the disease syndrome linked to FeLV infection. Furthermore feline leukemia is the first mammalian cancer for which vaccines have been developed and which are marketed by commercial companies in many countries of the world.
Gene Therapy and Small Molecules Used in the Treatment of Cystic Fibrosis
Published in Yashwant Pathak, Gene Delivery, 2022
Manish P. Patel, Uma G. Daryai, Mansi N. Athalye, Praful D. Bharadia, Jayvadan Patel
Other viruses used are Human (HIV), simian (SIV) and feline (FIV) immunodeficiency virus, as well as equine infectious anemia virus (EIAV). Vector platforms are being developed for cystic fibrosis gene therapy. As these vectors do not have a natural tropism for the lung, pseudotyping with appropriate envelope proteins is required to achieve efficient transduction. The vesicular stomatitis virus G (VSVG) protein, which is widely used, does not transduce airway epithelium efficiently via the apical membrane, but the transduction efficiency of vesicular stomatitis virus G can be increased by pre-administration of the tight junction openers that allow access of the virus to the basolateral membrane (Griesenbach, Pytel, and Alton, 2015).
Sterically stabilized recombined HDL composed of modified apolipoprotein A-I for efficient targeting toward glioma cells
Published in Drug Delivery, 2020
Jin Li, Mengmeng Han, Jianfei Li, Zhiming Ge, Qianqian Wang, Kai Zhou, Xiaoxing Yin
The apos and delipidated FIV precipitate were both identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) as described previously (Holmquist and Carlson, 1977). The gels were photographed with gel image system after completion of electrophoresis (GelDoc 2000, Bio-Rad, Hercules, CA). The molecular weight (MW) of extracted protein was estimated through linear regression between migrated distance and logarithm of MW of standard marker protein. ApoA-I bounded in the extracted apos was also confirmed by Western blotting. The sample separated using SDS-PAGE was electrophoretically transferred to membranes (100 V, 4 °C, 90 min). ApoA-I was detected with a polyclonal goat anti-human apoA-I antibody, accompanied by a horseradish peroxidase-conjugated donkey anti-goat IgG. Detection was performed using the enhanced chemiluminescence (ECL) method.
Emerging gene therapies for cystic fibrosis
Published in Expert Review of Respiratory Medicine, 2019
Kamran M. Miah, Stephen C. Hyde, Deborah R. Gill
Lentiviral vectors based on Human, Simian or Feline Immunodeficiency Viruses (HIV, SIV, and FIV, respectively) offer a promising gene therapy platform. Lentiviral vectors are capable of transducing dividing and non-dividing cells, including terminally differentiated airway epithelia [100], and integrating into the genome to permit long-term transgene expression in vivo. Lentiviral vectors have largely replaced γ-retroviral vectors, which historically have been widely used but lack the ability to transduce non-dividing cells, and unfortunately caused T cell acute lymphoblastic leukemia in a small number of X-linked SCID patients as a result of insertional mutagenesis [101]. Genetic analysis of the malignant cells in these patients showed that the γ-retroviral vector had integrated within or near tumor-promoting genes (mainly the LIM domain only-2 gene, LMO2) causing transcriptional activation. Self-inactivating (SIN) lentiviral vectors lack the long-terminal repeat enhancer sequences demonstrated to be responsible for this activation; and, show a preference to integrate into random intronic sequences rather than transcriptional start sites as preferred by γ-retroviral vectors. Crucially, lentiviral vectors have, to-date, not exhibited inadvertent oncogenesis, and both ex vivo and in vivo clinical trials show the platform to be generally safe [102,103]. As with rAAV, the ability to alter (or ‘pseudotype’) the lentiviral vector surface glycoprotein(s) permits expansion of the vectors’ cell targeting capabilities (Figure 3) [104–117].
Nontoxic fraction of scorpion venom reduces bacterial growth and inflammatory response in a mouse model of infection
Published in Toxin Reviews, 2021
Khedidja Zerouti, Dalila Khemili, Fatima Laraba-Djebari, Djelila Hammoudi-Triki
The chromatographic fraction FIV was tested in vivo for its antimicrobial activity in murine peritonitis model. Male NMRI mice (20–25 g) obtained from the animal breeding at the Pasteur Institute of Algeria are used. Animals had free access to food and water ad libitum and were housed under a regular 12 h light/12 h dark cycle. Procedures for animal experiments were conducted according to the European Community rules of the Ethical Committee for Animal Welfare.