Emergence of a Complex Relationship between HIV-1 and the microRNA Pathway

Abstract

SummaryRecent experimental evidences support the existence of an increasingly complex and multifaceted interaction between viruses and the microRNA-guided RNA silencing machinery of human cells. The discovery of small interfering RNAs (siRNAs), which are designed to mediate cleavage of specific messenger RNAs (mRNAs), prompted virologists to establish therapeutic strategies based on siRNAs with the aim to suppress replication of several viruses, including human immunodeficiency virus type 1 (HIV-1). It has been appreciated only recently that viral RNAs can also be processed endogenously by the microRNA-generating enzyme Dicer or recognized by cellular miRNAs, in processes that could be viewed as an adapted antiviral defense mechanism. Known to repress mRNA translation through recognition of specific binding sites usually located in their 3′ untranslated region, miRNAs of host or viral origin may exert regulatory effects towards host and/or viral genes and influence viral replication and/or the host response to viral infection. This article summarizes our current state of knowledge on the relationship between HIV-1 and miRNA-guided RNA silencing, and discusses the different aspects of their interaction.

The HIV-1 Nef Protein Binds Argonaute-2 and Functions as a Viral Suppressor of RNA Interference

“…Finally, viral transcripts have been co-localized with RNAi effector proteins in the P bodies [13]. Thus, cellular miRNAs affect HIV-1 replication, either through direct targeting of viral RNAs [16] or through targeting of cellular RNAs necessary for viral replication [17].…”

“…The HIV-1 Tat protein was reported to suppress RNAi through a direct, RNA-dependent interaction and inhibition of Dicer or, alternatively, through the sequestration of mature miRNAs [17]. It has been suggested that binding of the cellular protein TRBP to the structured TAR elements present in HIV-1 transcripts competitively inhibits the activity of TRBP as a co-factor for Dicer, leading to reduced miRNA processing [19].…”

The role of microRNAs in HIV infection

“…After cell entry and uncoating, the viral genetic material is reverse transcribed (RT) into cDNA by RT enzyme and integrated as double-strand DNA into the host genome before directing viral gene expression. HIV-1 relies on the cellular transcription and translation machineries for the synthesis of viral genomic proteins [22]. In most cases, HIV-1 successfully hijacks cellular pathways and bypasses restriction factors for optimal replication leading to continuous rounds of infection, replication and cell death.…”

Expression Analysis of Cellular Mir-29a and mir-29b in HIV Positive Patients

“…The key area of guide strand, a 6-8 nucleotides region, is situated at the 5'-end of the guide strand. Binding of this area to complementary sequence in the 3'UTR of mRNA activates the RISC complex and depletes or inhibits the translation of mRNA (1,(4)(5)(6)(7). MiRNA expression changes in viral infections that indicates their important role in the interaction between virus and host (8).…”

“…MiRNA expression changes in viral infections that indicates their important role in the interaction between virus and host (8). In addition to the protein-RNA and RNA-RNA interactions, recent studies have revealed a remarkable correlation between the viral proteins involved in the pathogenesis of HIV-1 and RNA silencing, similar to the tat and TRBP relation (5). It has been demonstrated that during viral infection, some proteins with 24/ Expression Analysis of Cellular.…”