Research

HIV possesses the unique ability to encode its own microRNAs (miRNAs), which play critical roles in regulating viral replication and host interactions. Viral miRNAs such as hiv1-miR-H1 and TAR-derived miRNAs enhance replication by modulating host gene expression, influencing apoptosis, and controlling transcription. In parallel, host cellular miRNAs exhibit dual roles-some suppress viral replication as part of the host defense, while others are hijacked by HIV proteins like TAT to promote viral transcription, immune evasion, and persistence. Together, these viral and host miRNA-mediated mechanisms finely tune the balance between viral suppression and propagation, shaping the course of HIV infection and offering insights into potential therapeutic targets.

During Herpes Simplex Virus (HSV) infection, a complex post-transcriptional regulatory landscape emerges, governed by both host and viral microRNAs (miRNAs). The host cell deploys endogenous miRNAs as an antiviral defense. For example, miR-101 is shown to target the viral ICP4 transcript, inhibiting its translation and thereby suppressing a key immediate-early protein required for the lytic cascade. Concurrently, other host miRNAs like miR-23a target cellular factors such as IRF1 (Interferon Regulatory Factor 1), attempting to modulate the host's own immune and antiviral signaling pathways.To counteract this, HSV expresses its own set of viral miRNAs (v-miRNAs) that manipulate host gene expression to favor viral replication and immune evasion. The diagram shows HSV-miR-H27 and miR-7704 targeting the host factor KLHL24, which subsequently modulates the NF-kB pathway - a central regulator of inflammation and immunity. Other v-miRNAs and viral proteins, like HSV p40, interact with the host translational machinery. This interaction, along with host factors like GRSP1, facilitates the translation of viral proteins by the host ribosome.This intricate interplay represents a molecular "arms race," where host miRNAs attempt to restrict viral gene expression and replication, while viral miRNAs actively suppress these defenses and hijack host pathways to establish a successful infection.

During Hepatitis C Virus (HCV) replication, the virion initiates infection by binding to specific host receptors like CD-81 and OCLN, leading to membrane fusion and endocytosis. This entry process itself is modulated by host microRNAs that can target the expression of these essential receptors. Once inside the cytoplasm, the viral positive-sense ssRNA is released and serves as a template for translation, a step heavily regulated by a large network of host miRNAs, most notably miR-122, which is crucial for stabilizing the viral genome and promoting its replication.

The resulting polyprotein is cleaved, and the viral RNA is recruited to specialized endoplasmic reticulum-derived membranes to form the RNA replication complex. This core process is also a major battleground, with numerous host miRNAs (such as the Let-7 family and miR-199a) attempting to suppress viral amplification. As new viral genomes are synthesized, they are packaged during assembly and trafficked for release via exocytosis. These final maturation and egress steps are also surveilled and interfered with by another set of host miRNAs, including miR-17-5p. This creates a complex regulatory landscape where the host cell deploys distinct microRNA networks to target virtually every sequential stage of the HCV life cycle.