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Orchestrating the Selection and Packaging of Genomic RNA by Retroviruses: An Ensemble of Viral and Host Factors

View Article: PubMed Central - PubMed

ABSTRACT

Infectious retrovirus particles contain two copies of unspliced viral RNA that serve as the viral genome. Unspliced retroviral RNA is transcribed in the nucleus by the host RNA polymerase II and has three potential fates: (1) it can be spliced into subgenomic messenger RNAs (mRNAs) for the translation of viral proteins; or it can remain unspliced to serve as either (2) the mRNA for the translation of Gag and Gag–Pol; or (3) the genomic RNA (gRNA) that is packaged into virions. The Gag structural protein recognizes and binds the unspliced viral RNA to select it as a genome, which is selected in preference to spliced viral RNAs and cellular RNAs. In this review, we summarize the current state of understanding about how retroviral packaging is orchestrated within the cell and explore potential new mechanisms based on recent discoveries in the field. We discuss the cis-acting elements in the unspliced viral RNA and the properties of the Gag protein that are required for their interaction. In addition, we discuss the role of host factors in influencing the fate of the newly transcribed viral RNA, current models for how retroviruses distinguish unspliced viral mRNA from viral genomic RNA, and the possible subcellular sites of genomic RNA dimerization and selection by Gag. Although this review centers primarily on the wealth of data available for the alpharetrovirus Rous sarcoma virus, in which a discrete RNA packaging sequence has been identified, we have also summarized the cis- and trans-acting factors as well as the mechanisms governing gRNA packaging of other retroviruses for comparison.

No MeSH data available.


Related in: MedlinePlus

Potential subcellular sites of the initial Gag–gRNA interaction. Gag and the vRNA may first interact: (1) in the nucleus; (2) along the cytoplasmic face of the nuclear envelope; (3) at the microtubule organizing center (MTOC; yellow); (4) in the cytoplasm; or (5) at the plasma membrane. In each case, the viral ribonucleoprotein complex binds to the plasma membrane and interacts with other Gag proteins to form a virion that (6) buds from the plasma membrane.
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viruses-08-00257-f003: Potential subcellular sites of the initial Gag–gRNA interaction. Gag and the vRNA may first interact: (1) in the nucleus; (2) along the cytoplasmic face of the nuclear envelope; (3) at the microtubule organizing center (MTOC; yellow); (4) in the cytoplasm; or (5) at the plasma membrane. In each case, the viral ribonucleoprotein complex binds to the plasma membrane and interacts with other Gag proteins to form a virion that (6) buds from the plasma membrane.

Mentions: The discovery that RSV Gag nuclear trafficking played a role in efficient gRNA encapsidation is novel to the field [79] (Figure 3). Since then, advances in microscopy and other methods have allowed other researchers to observe nuclear trafficking events of other retroviral and retrotransposon Gag proteins (reviewed in [162]). Previously, the Gag protein of the simple retrovirus MLV was detected within the nucleus of infected NIH3T3 cells [163]. Subcellular fractionations and immunoelectron microscopy staining for MLV Gag revealed that approximately 18% of the Gag protein was present within the nucleus of infected cells. It was proposed that nuclear MLV Gag could play a role in packaging the genomic RNA, but no experiments were done to test that idea.


Orchestrating the Selection and Packaging of Genomic RNA by Retroviruses: An Ensemble of Viral and Host Factors
Potential subcellular sites of the initial Gag–gRNA interaction. Gag and the vRNA may first interact: (1) in the nucleus; (2) along the cytoplasmic face of the nuclear envelope; (3) at the microtubule organizing center (MTOC; yellow); (4) in the cytoplasm; or (5) at the plasma membrane. In each case, the viral ribonucleoprotein complex binds to the plasma membrane and interacts with other Gag proteins to form a virion that (6) buds from the plasma membrane.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035971&req=5

viruses-08-00257-f003: Potential subcellular sites of the initial Gag–gRNA interaction. Gag and the vRNA may first interact: (1) in the nucleus; (2) along the cytoplasmic face of the nuclear envelope; (3) at the microtubule organizing center (MTOC; yellow); (4) in the cytoplasm; or (5) at the plasma membrane. In each case, the viral ribonucleoprotein complex binds to the plasma membrane and interacts with other Gag proteins to form a virion that (6) buds from the plasma membrane.
Mentions: The discovery that RSV Gag nuclear trafficking played a role in efficient gRNA encapsidation is novel to the field [79] (Figure 3). Since then, advances in microscopy and other methods have allowed other researchers to observe nuclear trafficking events of other retroviral and retrotransposon Gag proteins (reviewed in [162]). Previously, the Gag protein of the simple retrovirus MLV was detected within the nucleus of infected NIH3T3 cells [163]. Subcellular fractionations and immunoelectron microscopy staining for MLV Gag revealed that approximately 18% of the Gag protein was present within the nucleus of infected cells. It was proposed that nuclear MLV Gag could play a role in packaging the genomic RNA, but no experiments were done to test that idea.

View Article: PubMed Central - PubMed

ABSTRACT

Infectious retrovirus particles contain two copies of unspliced viral RNA that serve as the viral genome. Unspliced retroviral RNA is transcribed in the nucleus by the host RNA polymerase II and has three potential fates: (1) it can be spliced into subgenomic messenger RNAs (mRNAs) for the translation of viral proteins; or it can remain unspliced to serve as either (2) the mRNA for the translation of Gag and Gag–Pol; or (3) the genomic RNA (gRNA) that is packaged into virions. The Gag structural protein recognizes and binds the unspliced viral RNA to select it as a genome, which is selected in preference to spliced viral RNAs and cellular RNAs. In this review, we summarize the current state of understanding about how retroviral packaging is orchestrated within the cell and explore potential new mechanisms based on recent discoveries in the field. We discuss the cis-acting elements in the unspliced viral RNA and the properties of the Gag protein that are required for their interaction. In addition, we discuss the role of host factors in influencing the fate of the newly transcribed viral RNA, current models for how retroviruses distinguish unspliced viral mRNA from viral genomic RNA, and the possible subcellular sites of genomic RNA dimerization and selection by Gag. Although this review centers primarily on the wealth of data available for the alpharetrovirus Rous sarcoma virus, in which a discrete RNA packaging sequence has been identified, we have also summarized the cis- and trans-acting factors as well as the mechanisms governing gRNA packaging of other retroviruses for comparison.

No MeSH data available.


Related in: MedlinePlus