SRSF1 RNA Recognition Motifs Are Strong Inhibitors of HIV-1 Replication.
J Virol
; 89(12): 6275-86, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25855733
ABSTRACT
UNLABELLED Replication of the integrated HIV-1 genome is tightly regulated by a series of cellular factors. In previous work we showed that transactivation of the HIV-1 promoter is regulated by the cellular splicing factor SRSF1. Here we report that SRSF1 can downregulate the replication of B, C, and D subtype viruses by >200-fold in a cell culture system. We show that viral transcription and splicing are inhibited by SRSF1 expression. Furthermore, SRSF1 deletion mutants containing the protein RNA-binding domains but not the arginine serine-rich activator domain can downregulate viral replication by >2,000-fold with minimal impact on cell viability and apoptosis. These data suggest a therapeutic potential for SRSF1 and its RNA-binding domains. IMPORTANCE Most drugs utilized to treat the HIV-1 infection are based on compounds that directly target proteins encoded by the virus. However, given the high viral mutation rate, the appearance of novel drug-resistant viral strains is common. Thus, there is a need for novel therapeutics with diverse mechanisms of action. In this study, we show that the cellular protein SRSF1 is a strong inhibitor of viral replication. Furthermore, expression of the SRSF1 RNA-binding domains alone can inhibit viral replication by >2,000-fold in multiple viral strains without impacting cell viability. Given the strong antiviral properties of this protein, the RNA-binding domains, and the minimal effects observed on cell metabolism, further studies are warranted to assess the therapeutic potential of peptides derived from these sequences.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
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RNA Viral
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Proteínas Nucleares
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HIV-1
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Proteínas de Ligação a RNA
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Interações Hospedeiro-Patógeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article