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Questions and Answers
What is the primary method by which HIV enters its target cells?
What is the primary method by which HIV enters its target cells?
HIV can replicate in CD4+ T cells and macrophages.
HIV can replicate in CD4+ T cells and macrophages.
True
Name one type of animal model used for HIV research.
Name one type of animal model used for HIV research.
Humanized mice
The first step in the HIV pathogenesis involves viral entry through receptors such as ______.
The first step in the HIV pathogenesis involves viral entry through receptors such as ______.
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Which of the following is NOT a cellular protein that supports HIV replication?
Which of the following is NOT a cellular protein that supports HIV replication?
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Match the following HPV cell models with their description:
Match the following HPV cell models with their description:
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There is an ideal animal model for simulating all aspects of HIV infection in humans.
There is an ideal animal model for simulating all aspects of HIV infection in humans.
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What are the technical challenges associated with creating humanized models for HIV research?
What are the technical challenges associated with creating humanized models for HIV research?
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Study Notes
HIV Pathogenesis
- Viral Entry: HIV enters target cells via CD4 and either CCR5 or CXCR4, interacting with envelope glycoprotein.
- Reverse Transcription: The viral RNA is reverse transcribed into DNA after fusion and uncoating.
- Viral Integration: The pre-integration complex enters the nucleus, integrating the viral DNA into the host genome.
- Viral Replication & Protein Production: Host enzymes transcribe viral DNA into mRNA, which travels to the cytoplasm for protein synthesis and subsequent virion maturation. HIV-1 and HIV-2 replicate in CD4+ T cells and macrophages, spreading through bodily fluids.
Cellular Proteins Supporting Viral Replication
- Receptors and Co-receptors: CD4, CCR5, and CXCR4 are essential receptors and co-receptors for HIV replication.
- Transcription Factors: Cyclin T1 and other nuclear export factors (CRM1/EXP1) play a role in transcription.
- Budding Proteins: Proteins involved in the ESCRT pathway facilitate nascent viral particle budding.
Animal Models for HIV Research
- Direct Injection of HIV-1: Small animal models (like humanized mice) and non-human primate models (African monkeys) are used.
Limitations of Animal Models
- Lack of Ideal Model: No animal perfectly replicates all aspects of HIV infection in humans.
- Ethical and Legal Restrictions: The use of human fetal tissues in animal models is ethically and legally bound.
- Technical Challenges: Establishing humanized models requires advanced technologies and skills.
In Vitro HPV Models
- Cell Lines: HeLa, SiHa, and CaSki cell lines derived from cervical cancer patients are models.
- Organotypic Cultures: Proliferating keratinocytes cultured in a dermal-equivalent support are used to mimic HPV-induced squamous lesions. These cultures are better than traditional cell lines to interpret histological features.
In Vivo HPV Models
- Animal Models: Rabbit, dog, and bovine models exist.
- K14-HPV16-transgenic Mice: These models study carcinogenesis and immune modulation using the human keratin-14 promoter/enhancer. Chronic estrogen administration promotes malignant transformation in the model. This is a landmark study in this model.
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Description
Explore the complex processes of HIV pathogenesis, including viral entry, reverse transcription, integration, and replication. Understand the cellular proteins and receptors that support viral replication and how HIV spreads through the body.