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In this visual lecture Dr. Aizaz talks about Replicative cycle of poxviruses and Tecovirimat Life cycle is the series of changes that the organism goes through after it enters the cell and then it forms a new generation of virus which in turn infect more cells. Since the viruses aren’t considered a true living thing because they cannot survive outside the host, the term replicative cycle is used rather than “life cycle” The replicative cycles of both monkeypox, as well as the smallpox virus, are based on studies done on vaccinia virus which is a virus belonging to same genus. It is presumed that smallpox and monkeypox viruses follow the same pattern of replicative cycle. There are two types of poxviruses particles. One is covered with the double envelopes is called extracellular virion. The other type is covered by a single envelope and is called mature virion. When the extracellular virion’s outer membrane, via its tubules, interacts with the GAGs [need more info on GAGs] of the cell [which cell], the outer membrane is spontaneously disrupted, such that the inner membrane (inner envelope) is exposed. This inner membrane than fused with cell membrane and the nucleocapsid core along with lateral bodies, is ferried inside the cell. The mature virion has a single membrane which can directly fuse with the cell membrane and the nucleocapsid core is, in turn, transported into the cell. The mature virion can also be endocytosed inside the cell. It binds with a particular receptor [GAGs] on the cell membrane and the part of membrane pinches inward to form vesicle containing virion. It later sort of hatches out into the cytoplasm. The virus cannot do much without expressing its genome, the DNA. So it must expose the DNA. The problem is that it is coated the core. To uncoat it needs certain proteins. The virus brings its own DNA dependent RNA polymerase that forms mRNA for some early proteins including those that are required for uncoating. These mRNA transcripts are very small and are sent out of the capsid core into the cytoplasm. Here, it uses the host’s cytoplasmic ribosomes to form proteins. A few of the early proteins fully uncoat the viral DNA. The viral DNA also contain gene for DNA polymerase / replicase, that creates a number of copies of the DNA to packed in the next generation virus particles. The structural proteins like core proteins and the proteins of lateral bodies are also synthesized within the cytoplasm and they bind with the one of the copies of DNA to assemble an immature virus particle, that isn’t yet enveloped. Other proteins like RNA polymerase are also packed within the nucleocapsid core. Some of the viral proteins are studded into Endoplasmic reticulum and these portions of ER buds off and surround the immature virion to form the mature virion. Some of the mature virions are wrapped by another membrane from the Golgi apparatus. This virion is then exocytosed out of the cell as an extracellular virion. The mature virion is released as a result of cell death when cells are broken (cell lysis). These released virions are now ready to infect other cells and as they do so the cycle continues. The entire replicative cycle of poxvirus occurs within the cytoplasm