# Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication

## TL;DR

This review explores how retroviruses replicate, highlighting new discoveries and their impact on molecular biology and gene therapy.

## Contribution

The paper integrates classical and emerging insights on retroviral replication mechanisms and their implications for biology and medicine.

## Key findings

- Recent advances in understanding nuclear trafficking of capsids and reverse transcription are reshaping classical models.
- The structural and functional roles of viral proteins like Gag are redefined in the context of assembly and maturation.
- Emerging insights into RNA nuclear export and selective genome packaging are detailed.

## Abstract

Retroviruses are exclusive group of positive-sense RNA viruses defined by their ability to reverse transcribe their RNA genome and integrate it into the host’s chromosomal DNA. This distinctive replication strategy enables persistent infection and has profoundly shaped our understanding of molecular biology, gene regulation, and evolution. Retroviruses have contributed to landmark discoveries, including the identification of oncogenes, mechanisms of transcriptional control, and the development of gene therapy vectors. This review provides an updated overview of retroviral molecular biology, emphasizing the coordinated steps of the viral life cycle and emerging insights that are reshaping classical models. It explores virion structure, genome organization, and the interplay of cis-acting sequences and trans-acting factors that govern replication. Special focus is given to recent advances in understanding nuclear trafficking of capsids, spatial dynamics of reverse transcription and integration leading to provirus formation, RNA nuclear export, and selective genome packaging. The structural and functional roles of viral proteins, particularly Gag, are discussed in the context of assembly and maturation. By integrating foundational concepts with new discoveries, this review highlights the molecular sophistication of retroviral replication and identifies outstanding questions that guide future research, with implications extending to antiviral strategies, gene therapy, cancer biology, and evolution.

This review unites emerging discoveries with classical understanding on how retroviruses replicate and interact with their hosts, offering fresh insights into molecular virology and host cell biology.