Encapsidation and transduction of cellular genes by retroviruses

Abstract

Retroviruses normally package their genomic RNA with high fidelity. However, the fidelity is apparently imperfect, since some cellular mRNA is present in standard retrovirus particles. Further, transcripts originating in the 5′ LTR of the integrated provirus sometimes extend beyond the 3′ end of the provirus, resulting in the production of chimeric RNAs containing both viral and cellular sequences. These RNAs can be exported to the cytoplasm and packaged into assembling virus particles. When such particles infect a new host cell, reverse transcriptase may copy the cellular sequences, as well as viral sequences, into DNA. In turn, recombinational events during reverse transcription can result in the incorporation of cellular sequences into retroviral genomes. If the cellular sequences encode proteins involved in the control of cell growth, then the high or inappropriate expression of these sequences as part of the retroviral genome may cause the malignant transformation of the infected cell. Viruses of this type, that transduce cellular transforming genes, are known as acute transforming viruses. They can only arise in animals infected with replication-competent retroviruses, and in general cannot produce progeny viruses without replication-competent "helper" viruses. Since they are produced by a complex, multi-step pathway, acute transforming viruses are only generated at very low frequencies.