Impact of Nuclear Export Pathway on Cytoplasmic HIV-1 RNA Transport Mechanism and Distribution
| Autor: | Jianbo Chen, Wei-Shau Hu, David Q. Sun, Olga A. Nikolaitchik, Ben Berkhout, Chijioke N. Umunnakwe, Atze T. Das, Vinay K. Pathak |
|---|---|
| Přispěvatelé: | Medical Microbiology and Infection Prevention, AII - Infectious diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cytoplasm
Cytoplasmic Viral protein Nuclear export viruses Active Transport Cell Nucleus RNA transport HIV Infections In situ hybridization Distribution medicine.disease_cause Microbiology RNA Transport Host-Microbe Biology NXF1 Diffusion 03 medical and health sciences Virology medicine Humans Nuclear export signal 030304 developmental biology Cell Nucleus 0303 health sciences Chemistry 030302 biochemistry & molecular biology RNA virus diseases Translation (biology) QR1-502 Cell biology Gene Products rev HIV-1 RNA Viral Transport mechanism Research Article |
| Zdroj: | mBio, 11(6):e01578-20, 1-18. American Society for Microbiology mBio, Vol 11, Iss 6 (2020) mBio |
| ISSN: | 2161-2129 |
| Popis: | The unspliced HIV-1 full-length RNA (HIV-1 RNA) is packaged into virions as the genome and is translated to generate viral structural proteins and enzymes. To serve these functions, HIV-1 RNA must be exported from the nucleus to the cytoplasm. It was recently suggested that export pathways used by HIV-1 RNA could affect its cytoplasmic transport mechanisms and distribution. In the current report, we examined the HIV-1 RNA transport mechanism by following the movement of individual RNAs and identifying the distribution of RNA using in situ hybridization. Our results showed that whether exported by the CRM1 or NXF1 pathway, HIV-1 RNAs mainly use diffusion for cytoplasmic travel. Furthermore, HIV-1 RNAs exported using the CRM1 or NXF1 pathway are well mixed in the cytoplasm and do not display export pathway-specific clustering near centrosomes. Thus, the export pathways used by HIV-1 RNAs do not alter the cytoplasmic transport mechanisms or distribution. HIV-1 full-length RNA (referred to as HIV-1 RNA here) serves as the viral genome in virions and as a template for Gag/Gag-Pol translation. We previously showed that HIV-1 RNA, which is exported via the CRM1 pathway, travels in the cytoplasm mainly through diffusion. A recent report suggested that the export pathway used by retroviral RNA could affect its cytoplasmic transport mechanism and localization. HIV-1 RNA export is directed by the viral protein Rev and the cis-acting element, Rev response element (RRE). When Rev/RRE is replaced with the constitutive transport element (CTE) from Mason-Pfizer monkey virus (MPMV), HIV-1 RNA is exported through the NXF1 pathway. To determine the effects of the export pathway on HIV-1 RNA, we tracked individual RNAs and found that the vast majority of cytoplasmic HIV-1 RNAs travel by diffusion regardless of the export pathway. However, CTE-containing HIV-1 RNA diffuses at a rate slower than that of RRE-containing HIV-1 RNA. Using in situ hybridization, we analyzed the subcellular localizations of HIV-1 RNAs in cells expressing a CTE-containing and an RRE-containing provirus. We found that these two types of HIV-1 RNAs have similar subcellular distributions. HIV-1 RNA exported through the NXF1 pathway was suggested to cluster near centrosomes. To investigate this possibility, we measured the distances between individual RNAs to the centrosomes and found that HIV-1 RNAs exported through different pathways do not exhibit significantly different distances to centrosomes. Therefore, HIV-1 RNAs exported through CRM1 and NXF1 pathways use the same RNA transport mechanism and exhibit similar cytoplasmic distributions. |
| Databáze: | OpenAIRE |
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