دورية أكاديمية
أعرض في EDS

Specific Guanosines in the HIV-2 Leader RNA are Essential for Efficient Viral Genome Packaging.

التفاصيل البيبلوغرافية
العنوان: Specific Guanosines in the HIV-2 Leader RNA are Essential for Efficient Viral Genome Packaging.
المؤلفون: Umunnakwe CN; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Duchon A; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Nikolaitchik OA; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Rahman SA; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Liu Y; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Chen J; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Tai S; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Pathak VK; Viral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Hu WS; Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: Wei-Shau.Hu@nih.gov.
المصدر: Journal of molecular biology [J Mol Biol] 2021 Jan 22; Vol. 433 (2), pp. 166718. Date of Electronic Publication: 2020 Nov 19.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
مواضيع طبية MeSH: 5' Untranslated Regions* , RNA, Viral* , Viral Genome Packaging*, Guanosine/*metabolism , HIV Infections/*metabolism , HIV Infections/*virology , HIV-2/*physiology, Base Sequence ; Cell Line ; Gene Expression Regulation, Viral ; Genome, Viral ; Humans ; Mutation ; Nucleic Acid Conformation ; Virus Assembly ; Virus Replication ; gag Gene Products, Human Immunodeficiency Virus/metabolism
مستخلص: HIV-2, a human pathogen that causes acquired immunodeficiency syndrome, is distinct from the more prevalent HIV-1 in several features including its evolutionary history and certain aspects of viral replication. Like other retroviruses, HIV-2 packages two copies of full-length viral RNA during virus assembly and efficient genome encapsidation is mediated by the viral protein Gag. We sought to define cis-acting elements in the HIV-2 genome that are important for the encapsidation of full-length RNA into viral particles. Based on previous studies of murine leukemia virus and HIV-1, we hypothesized that unpaired guanosines in the 5' untranslated region (UTR) play an important role in Gag:RNA interactions leading to genome packaging. To test our hypothesis, we targeted 18 guanosines located in 9 sites within the HIV-2 5' UTR and performed substitution analyses. We found that mutating as few as three guanosines significantly reduce RNA packaging efficiency. However, not all guanosines examined have the same effect; instead, a hierarchical order exists wherein a primary site, a secondary site, and three tertiary sites are identified. Additionally, there are functional overlaps in these sites and mutations of more than one site can act synergistically to cause genome packaging defects. These studies demonstrate the importance of specific guanosines in HIV-2 5'UTR in mediating genome packaging. Our results also demonstrate an interchangeable and hierarchical nature of guanosine-containing sites, which was not previously established, thereby revealing key insights into the replication mechanisms of HIV-2.
(Published by Elsevier Ltd.)
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معلومات مُعتمدة: ZIA BC010814 United States ImNIH Intramural NIH HHS; ZIA BC011436 United States ImNIH Intramural NIH HHS
فهرسة مساهمة: Keywords: RNA; encapsidation; guanosine; retroviruses; untranslated region
المشرفين على المادة: 0 (5' Untranslated Regions)
0 (RNA, Viral)
0 (gag Gene Products, Human Immunodeficiency Virus)
12133JR80S (Guanosine)
تواريخ الأحداث: Date Created: 20201122 Date Completed: 20210426 Latest Revision: 20220716
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9168803
DOI: 10.1016/j.jmb.2020.11.017
PMID: 33221337
قاعدة البيانات: MEDLINE
الوصف
تدمد:1089-8638
DOI:10.1016/j.jmb.2020.11.017