5′-Cap sequestration is an essential determinant of HIV-1 genome packaging
Pengfei Ding, Siarhei Kharytonchyk, Nansen Kuo, Emily Cannistraci, Hana Flores, Ridhi Chaudhary, Mitali Sarkar‐Tyson, Xinmei Dong, Alice Telesnitsky, Michael F. Summers
Abstract
Significance HIV-1 replication is critically dependent on the selective incorporation of viral RNA genomes into assembling virions. Although RNA elements that promote packaging have been identified, the determinants of authentic packaging fidelity and efficiency have until now remained unknown. The present studies show that genome selection is achieved by a bipartite mechanism that requires both dimerization-dependent exposure of packaging signals within the 5′ leader of the viral RNA and structural sequestration of the 5′ cap. Cap sequestration likely prevents capture by the cellular RNA processing and translation machinery, a mechanism that may help explain why some cellular RNA polymerase III transcripts that lack 5′ caps can parasitize virions. Cap sequestration may be commonly employed among RNA viruses that package 5′-capped genomes.