دورية أكاديمية
أعرض في EDS

Adaptation of HIV-1/HIV-2 Chimeras with Defects in Genome Packaging and Viral Replication.

التفاصيل البيبلوغرافية
العنوان: Adaptation of HIV-1/HIV-2 Chimeras with Defects in Genome Packaging and Viral Replication.
المؤلفون: Rawson JMO; Viral Recombination Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA., Nikolaitchik OA; Viral Recombination Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA., Yoo JA; Viral Recombination Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA., Somoulay X; Viral Recombination Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA., Brown MA; Viral Recombination Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA., Mbuntcha Bogni FS; Viral Recombination Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA., Pathak VK; Viral Mutation Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA., Soheilian F; Electron Microscopy Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Slack RL; Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory Universitygrid.189967.8 School of Medicine, Atlanta, Georgia, USA., Sarafianos SG; Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory Universitygrid.189967.8 School of Medicine, Atlanta, Georgia, USA., Hu WS; Viral Recombination Section, HIV Dynamics and Replication Program, NCI, Frederick, Maryland, USA.
المصدر: MBio [mBio] 2022 Oct 26; Vol. 13 (5), pp. e0222022. Date of Electronic Publication: 2022 Aug 29.
نوع المنشور: Journal Article; Research Support, N.I.H., Intramural; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: HIV-1*/metabolism, Humans ; HIV-2/genetics ; RNA, Viral/metabolism ; Chimera/metabolism ; Amino Acid Sequence ; Virus Replication ; Viral Proteins/metabolism ; Virus Assembly ; Genome, Viral
مستخلص: Frequent recombination is a hallmark of retrovirus replication. In rare cases, recombination occurs between distantly related retroviruses, generating novel viruses that may significantly impact viral evolution and public health. These recombinants may initially have substantial replication defects due to impaired interactions between proteins and/or nucleic acids from the two parental viruses. However, given the high mutation rates of retroviruses, these recombinants may be able to evolve improved compatibility of these viral elements. To test this hypothesis, we examined the adaptation of chimeras between two distantly related human pathogens: HIV-1 and HIV-2. We constructed HIV-1-based chimeras containing the HIV-2 nucleocapsid (NC) domain of Gag or the two zinc fingers of HIV-2 NC, which are critical for specific recognition of viral RNA. These chimeras exhibited significant defects in RNA genome packaging and replication kinetics in T cells. However, in some experiments, the chimeric viruses replicated with faster kinetics when repassaged, indicating that viral adaptation had occurred. Sequence analysis revealed the acquisition of a single amino acid substitution, S18L, in the first zinc finger of HIV-2 NC. This substitution, which represents a switch from a conserved HIV-2 residue to a conserved HIV-1 residue at this position, partially rescued RNA packaging and replication kinetics. Further analysis revealed that the combination of two substitutions in HIV-2 NC, W10F and S18L, almost completely restored RNA packaging and replication kinetics. Our study demonstrates that chimeras of distantly related retroviruses can adapt and significantly enhance their replication by acquiring a single substitution. IMPORTANCE Novel retroviruses can emerge from recombination between distantly related retroviruses. Most notably, HIV-1 originated from zoonotic transmission of a novel recombinant (SIV cpz ) into humans. Newly generated recombinants may initially have significant replication defects due to impaired interactions between viral proteins and/or nucleic acids, such as between cis- and trans -acting elements from the two parental viruses. However, provided that the recombinants retain some ability to replicate, they may be able to adapt and repair the defective interactions. Here, we used HIV-1 and HIV-2 Gag chimeras as a model system for studying the adaptation of recombinant viruses. We found that only two substitutions in the HIV-2 NC domain, W10F and S18L, were required to almost fully restore RNA genome packaging and replication kinetics. These results illustrate the extremely flexible nature of retroviruses and highlight the possible emergence of novel recombinants in the future that could pose a significant threat to public health.
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معلومات مُعتمدة: R01 AI146017 United States AI NIAID NIH HHS; HHSN261201500003I United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Gag; HIV-1; HIV-2; RNA packaging; adaptation; chimeric virus; evolution; lentivirus; nucleocapsid; recombination; replication; zinc finger
المشرفين على المادة: 0 (RNA, Viral)
0 (Viral Proteins)
تواريخ الأحداث: Date Created: 20220829 Date Completed: 20221028 Latest Revision: 20230104
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9600866
DOI: 10.1128/mbio.02220-22
PMID: 36036631
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.02220-22