دورية أكاديمية
أعرض في EDS

Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo.

التفاصيل البيبلوغرافية
العنوان: Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo.
المؤلفون: Francella N, Elliott ST, Yi Y, Gwyn SE, Ortiz AM, Li B, Silvestri G, Paiardini M, Derdeyn CA, Collman RG; Department of Medicine, University of Pennsylvania Perelman School of Medicine, 522 Johnson Pavilion, 36th & Hamilton Walk, Philadelphia, PA, USA. collmanr@mail.med.upenn.edu.
المصدر: Retrovirology [Retrovirology] 2013 Nov 12; Vol. 10, pp. 133. Date of Electronic Publication: 2013 Nov 12.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101216893 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-4690 (Electronic) Linking ISSN: 17424690 NLM ISO Abbreviation: Retrovirology Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2004-
مواضيع طبية MeSH: Virus Attachment*, Receptors, CCR5/*metabolism , Receptors, Virus/*metabolism , Simian Immunodeficiency Virus/*physiology , Viral Envelope Proteins/*metabolism, Animals ; CD4 Antigens/metabolism ; Macaca mulatta ; Mutant Proteins/genetics ; Mutant Proteins/metabolism ; Mutation ; Simian Immunodeficiency Virus/genetics ; Viral Envelope Proteins/genetics
مستخلص: Background: HIV and SIV generally require CD4 binding prior to coreceptor engagement, but Env can acquire the ability to use CCR5 independently of CD4 under various circumstances. The ability to use CCR5 coupled with low-to-absent CD4 levels is associated with enhanced macrophage infection and increased neutralization sensitivity, but the additional features of these Envs that may affect cell targeting is not known.
Results: Here we report that CD4-independent SIV variants that emerged in vivo in a CD4+ T cell-depleted rhesus macaque model display markedly decreased plasticity of co-receptor use. While CD4-dependent Envs can use low levels of macaque CCR5 for efficient entry, CD4-independent variants required high levels of CCR5 even in the presence of CD4. CD4-independent Envs were also more sensitive to the CCR5 antagonist Maraviroc. CD4-dependent variants mediated efficient entry using human CCR5, whereas CD4-independent variants had impaired use of human CCR5. Similarly, CD4-independent Envs used the alternative coreceptors GPR15 and CXCR6 less efficiently than CD4-dependent variants. Env amino acids D470N and E84K that confer the CD4-independent phenotype also regulated entry through low CCR5 levels and GPR15, indicating a common structural basis. Treatment of CD4-dependent Envs with soluble CD4 enhanced entry through CCR5 but reduced entry through GPR15, suggesting that induction of CD4-induced conformational changes by non-cell surface-associated CD4 impairs use of this alternative co-receptor.
Conclusions: CD4 independence is associated with more restricted coreceptor interactions. While the ability to enter target cells through CCR5 independently of CD4 may enable infection of CD4 low-to-negative cells such as macrophages, this phenotype may conversely reduce the potential range of targets such as cells expressing low levels of CCR5, conformational variants of CCR5, or possibly even alternative coreceptors.
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معلومات مُعتمدة: T32-AI007632 United States AI NIAID NIH HHS; P30-AI045008 United States AI NIAID NIH HHS; R01 MH061139 United States MH NIMH NIH HHS; P51-RR000165 United States RR NCRR NIH HHS; AI066998 United States AI NIAID NIH HHS; P30 CA016520 United States CA NCI NIH HHS; P51-OD011132 United States OD NIH HHS; AI091516 United States AI NIAID NIH HHS; MH61139 United States MH NIMH NIH HHS; AI58706 United States AI NIAID NIH HHS; R01 AI058706 United States AI NIAID NIH HHS; P30 AI045008 United States AI NIAID NIH HHS; R37 AI066998 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (CD4 Antigens)
0 (Mutant Proteins)
0 (Receptors, CCR5)
0 (Receptors, Virus)
0 (Viral Envelope Proteins)
تواريخ الأحداث: Date Created: 20131114 Date Completed: 20140707 Latest Revision: 20211021
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3833851
DOI: 10.1186/1742-4690-10-133
PMID: 24219995
قاعدة البيانات: MEDLINE
الوصف
تدمد:1742-4690
DOI:10.1186/1742-4690-10-133