Animal BT Studying Notes (5) PDF

What is the pathogenesis of HIV? 1) Viral Entry: a) HIV enters its target cells via CD4 and either CC-chemokine (CCR5) or CXC-chemokine receptor 4 (CXCR4) through interaction with envelope (Env) glycoprotein 2) Reverse Transcription: a) After fusion an...

What is the pathogenesis of HIV? 1) Viral Entry: a) HIV enters its target cells via CD4 and either CC-chemokine (CCR5) or CXC-chemokine receptor 4 (CXCR4) through interaction with envelope (Env) glycoprotein 2) Reverse Transcription: a) After fusion and uncoating, the viral RNA is then reverse transcribed into DNA 3) Viral Inegration: a) The ensuing pre-integration complex is imported into the nucleus, and the viral DNA is then integrated into the host genome 4) Viral replication & Protein production: a) Mediated by host enzymes, HIV DNA is transcribed to viral mRNAs b) These mRNAs are then exported to the cytoplasm where translation occurs to make viral proteins and eventually the mature virions Viruses that causes AIDS - HIV-1 & HIV-2; principally spread by bodily fluids & replicate in CD4+ T cells and macrophages Which cellular proteins supports the viral replication of HIV? 1) Receptors and co-receptors - CD4 and either CC-chemokine receptor 5 (CCR5) or CXC-chemokine receptor 4 (CXCR4) 2) Transcription factors (cyclin T1), nuclear export factors (CRM1; also known as EXP1) 3) Proteins that mediate budding of nascent viral particles (belonging to the ESCRT pathway) What type of animal models are used for HIV research and how are they being prepared? Direct injection of HIV-1 1) Small animal models a) Humanized mice 2) Non-human primate models a) Species of African monkeys What are the current limitations//barriers for the development of animal models for HIV research? - Lack of an ideal model: there is no animal model that perfectly mimics all aspects of HIV infection in humans - Ethical and legal restrictions: using human fetal tissues in mouse models is subject to ethical and legal restrictions - Technical challenges: Establishing humanized models requires complex technologies and advanced technical skills What are the in vitro models of HPV? - HeLa, SiHa, CaSki - cell lines obtained from cervical cancer patients - Organotypic cultures - proliferating keratinocytes cultured in a dermal-equivalent support; allows some degree of histological interpretation; may be used to mimic HPV-induced squamous lesions What are the in vivo models of HPV? - Rabbit, Dog, Bovine - K14-HPV16-transgenic mice: models for carcinogenesis and immune modulation - Under the control of the human keratin-14 promoter/enhancer - Landmark study in this model - chronic estrogen administration promotes malignant transformation of squamous epithelium of the cervix and vagina