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When a virus replicates, it has to create several copies of its genome to the "daughter viruses"? Where in the cell does this replication of the viral genome take place? And how?

In my book, they use HIV-viruses as an example, which I've understood is a retrovirus. The first steps they describe are attachment, entry and uncoating, which I understand. Then, the next step is integration, which they say start with that the RNA translates to DNA and the new DNA strand works as a template to create a dsDNA. dsDNA is then integrated in the host cells genome, and then after that the transcription and translation of virus protein can start. What I don't understand is when the replication of RNA strands take place? After the synthesis of protein, there is the assembly, where the protein and RNA build up new viruses. Where does the RNA come from? Does the replication take place before the integration? Or when the DNA is integrated in the host cell genome, at the same time as the protein synthesis?

For other types of virus, they say that the genome replicates by a "rolling circle mechanism"? Where does that take place? In the cytoplasm? In those cases, isn't the viral genome integrated in the host cells genome at all? They just use the host cells polymerase, ribosomes etc.? Is retro viruses the only viruses that integrates in the genome?

This became kind of long, but to summarize my questions:

  1. Retroviruses: Where and how does the replication of the RNA take place? Before or during integration of the host cell genome?
  2. Where does the replication of genome of other viruses (that use the rolling circle mechanism) take place? In the cytoplasm?
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    $\begingroup$ Welcome to SE Biology. I have no idea what your book is, but it has given you a limited and distorted view of viruses. There is a wide spectrum of viruses, with different sorts of genome — DNA, RNA, single and double-stranded, linear, circular and segmented. How and where they replicated differs accordingly. Retroviruses are a strange hybrid, and rolling-circle replication only applies to small circular viruses, so these seem an odd choice for a text. Read the general Wikipedia article and specific articles for viruses of interest… $\endgroup$
    – David
    Sep 21 at 13:46
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    $\begingroup$ …This should provide you with answers. If there is a particular aspect you do not understand, then you need to show that you have done some research in crafting a question about that specific problem. At the moment your question is several questions based on false premises. And rather than just asking questions, try to think about and rationalize the problem. Ask whether a virus uses its own replicative enzyme or that of the host. If it uses the host DNA polymerase, it needs to be in the nucleus to replicate. If not, it may not — although other considerations come into play with retroviruses. $\endgroup$
    – David
    Sep 21 at 13:51

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First Question:

Integration is essential for retroviruses, otherwise cDNA isn‘t transcribed efficiently into RNA (viral genome). Eucaryotic transcription requires multiple factors that are only present in the nucleus and work best when associated to genomic DNA (host). Retroviruses also lack an RNA-dependent RNA polymerase, which would replicate viral genome in the cytosol.

Craige & Bushman 2012:

Integration of a DNA copy of the viral genome into a host cell chromosome is an essential step in the retroviral replication cycle (Varmus et al. 1989; Coffin et al. 1997).

Textbook like reference Ref 1, Ref 2

The viral DNA is transported across the nucleus, where the HIV protein integrase integrates the HIV DNA into the host’s DNA. The host’s normal transcription machinery transcribes HIV DNA into multiple copies of new HIV RNA. Some of this RNA becomes the genome of a new virus, while the cell uses other copies of the RNA to make new HIV proteins.

For more details see Dutilleul et al. 2020

Once randomly integrated into the host cellular genome, HIV-1 gene expression is mainly regulated at the transcriptional level by hijacking the cellular RNA polymerase II (RNAPII) machinery. HIV-1 transcription initiates at the U3/R junction in the 5′-long terminal repeat (5′LTR) and is regulated by cellular transcription factors […]

So Replication happens after insertion of cDNA (complementary DNA, product of reverse transcription and second strand synthesis) into the host genome in the nucleus. Then transcription factors can bind the promoter and initiate elongation.

Second Question:

For DNA- viruses, some require integration into host genome, too. Interestingly, non-integrated viral DNA can populate the nucleus as dormant (circular) episomes (see viral latency, De Leo et al. 2020). Non-integrating DNA viruses often bring a DNA-dependent DNA polymerase and can replicate in the cytosol.

(If interested, see this review on viral polymerases that enable replication of viral genomes in the cytosol Choi 2016)

About Rolling Circle Replication:

Rolling circle replication is mainly found in procaryotic viruses (Phages). For eucaryotic viruses, rolling circle is pretty rare. The Geminivirus however, is one example of a non integrating DNA virus that replicates by rolling circle within the nuclei of plants. It seems that it relies heavily on nuclear factors for efficient DNA-Replication Castellano et al 1999

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  • $\begingroup$ @markur - There are varying definitions of "schoolroom knowledge". To me, much of medicine is "schoolroom knowledge", and as a molecular biologist, much of biochemistry is "schoolroom knowledge". On this site, answers are expected to be supported regardless of your level of education, so that others may evaluate your answer on its merits, not simply on your say-so. There is no argument from authority (well, one can make a case for that from sources, but research is better.) $\endgroup$ 2 days ago
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    $\begingroup$ @anongoodnurse I've removed my comment. The answer still seems a bit misleading to me (e.g.: part 2 talks about DNA viruses only, but then quotes a passage that's broader than that) but I think that's mostly from the misdirection and multiplicity of questions in the original post, as pointed out by David in other comments. $\endgroup$
    – Bryan Krause
    2 days ago
  • $\begingroup$ @BryanKrause - I see. I edited that part on polymerases to appear more as a side-note. I think it‘s a cool review that helps understand viral lifecycles in general. $\endgroup$
    – markur
    yesterday

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