1694 Nucleic Acids Research, 2010, Vol. 38, No. 5 Figure 9. Model summarizing that DExD/H proteins contribute to many steps in retroviral posttranscriptional gene expression and coordination of virus assembly. Nuclear export of HIV-1 Rev/Rev responsive element (RRE)-dependent HIV-1 RNA requires DDX3 with CRM1 nuclear export receptor (27). Alternatively, the nuclear export ribonucleoprotein (RNP) of completely spliced viral RNA involves superfamily members RBM15 and DBP5 and NXF1 nuclear export receptor (28,29). Eﬃcient viral translation requires DHX9/RNA helicase A [herein and (5)]. RNA helicase A recognizes structural features of virus 50 RNA terminus and possibly distal structures, and facilitates eﬃcient protein synthesis in an ATP-dependent manner (2). RNA helicase A also assembles into virions and supports virus infectivity, perhaps by promoting rearrangement of the viral RNP for reverse transcription or by carrying in a host cofactor (12). DDX24 promotes packaging of HIV-1 RNA (30). DISCUSSION RHA is an important host factor This report determined that RHA is necessary for two aspects of HIV-1 biology: RHA present in the infected cell facilitates eﬃcient translation of viral mRNA and RHA assembled into virus particles promotes infectivity of progeny virions. The virions are not deﬁcient in viral RNA, processed RT, nor the cellular cofactor LysRS. The results open the new issue of the possible interrelationship of RHA promoting viral mRNA translation and produc- tion of infectious virions. First, the results demonstrated that translation of HIV-1 gag mRNA is reliant on the ATP-dependent helicase activity of RHA. A straightforward model is that RHA interaction promotes RNP rearrangement to open the complex 50 UTR to eﬃcient ribosome scanning (Figure 9). We invoke ribosome scanning model instead of an internal ribosome entry site (IRES)-related mechanism because RHA has been shown to promote cap-dependent, but not cap-independent translation (5) and because the retroviral PCEs do not substitute for IRES in a bicistronic reporter RNA (5). We speculate that all HIV-1 transcripts require RHA for eﬃcient translation for two reasons: (i) all HIV-1 transcripts contain the similar highly complex 50 UTR (1), which includes the RU5 region that conveys PCE reporter activity and interacts with RHA (Figure 2) and was previously shown to be suﬃcient for RHA-dependent PCE activity (5); (ii) Vif, Rev and Nef protein levels are reduced by RHA down-regulation, con- sistent with translation down-regulation (Figure 7). These observations open new questions. First, what features of HIV-1 RU5 and possibly distal sequences are suﬃ- cient for the speciﬁc interaction with RHA. Second, is the ATP-dependent helicase activity of RHA necessary to promote virus infectivity. Attractive speculation is that helicase-dependent rearrangement of the 50 UTR involving RHA changes the activity of other cis-acting replication sequences in the 50 UTR, including the packaging signal. A simple model invokes an inverse relationship between translation and packaging eﬃciency. Herein RHA neutralizes structural features of the 50 UTR to promote eﬃcient ribosome scanning. However, the structural