Retrovirus translation initiation: Issues and hypotheses derived from study of HIV-1.
Human immunodeficiency virus type 1 (HIV-1) has a small, multifunctional genome that encodes a relatively large and complex proteome. The virus has adopted specialized post-transcriptional control mechanisms to maximize its coding capacity while economically maintaining the information stored in cis-acting replication sequences. The conserved features of the 5' untranslated region of all viral transcripts suggest they are poor substrates for cap-dependent ribosome scanning and provide a compelling rationale for internal initiation of translation. This article summarizes key experimental results of studies that have evaluated HIV-1 translation initiation. A model is discussed in which cap-dependent and cap-independent initiation mechanisms of HIV-1 co-exist to ensure viral protein production in the context of 1) structured replication motifs that inhibit ribosome scanning, and 2) alterations in host translation machinery in response to HIV-1 infection or other cellular stresses. We discuss key issues that remain to be understood and suggest parameters to validate internal initiation activity in HIV-1 and other retroviruses.
Yilmaz
Alper
A
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA.
Bolinger
Cheryl
C
Boris-Lawrie
Kathleen
K
D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
D012333:RNA, Messenger; D012367:RNA, Viral