Selective Pressure Against AUG Triplets in the 5´ Untranslated Region of Human Immunodeficiency Virus Type 1 Supports Cap-Dependent Translation Initiation Mechanism

2008 ◽  
pp. 17-24
Author(s):  
Sam Khalouei and Xuhua Xia
2003 ◽  
Vol 77 (5) ◽  
pp. 3020-3030 ◽  
Author(s):  
Ebbe Sloth Andersen ◽  
Rienk E. Jeeninga ◽  
Christian Kroun Damgaard ◽  
Ben Berkhout ◽  
Jørgen Kjems

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) particle contains two identical RNA strands, each corresponding to the entire genome. The 5′ untranslated region (UTR) of each RNA strand contains extensive secondary and tertiary structures that are instrumental in different steps of the viral replication cycle. We have characterized the 5′ UTRs of nine different HIV-1 isolates representing subtypes A through G and, by comparing their homodimerization and heterodimerization potentials, found that complementarity between the palindromic sequences in the dimerization initiation site (DIS) hairpins is necessary and sufficient for in vitro dimerization of two subtype RNAs. The 5′ UTR sequences were used to design donor and acceptor templates for a coupled in vitro dimerization-reverse transcription assay. We showed that template switching during reverse transcription is increased with a matching DIS palindrome and further stimulated proportional to the level of homology between the templates. The presence of the HIV-1 nucleocapsid protein NCp7 increased the template-switching efficiency for matching DIS palindromes twofold, whereas the recombination efficiency was increased sevenfold with a nonmatching palindrome. Since NCp7 did not effect the dimerization of nonmatching palindromes, we concluded that the protein most likely stimulates the strand transfer reaction. An analysis of the distribution of template-switching events revealed that it occurs throughout the 5′ UTR. Together, these results demonstrate that the template switching of HIV-1 reverse transcriptase occurs frequently in vitro and that this process is facilitated mainly by template proximity and the level of homology.


2008 ◽  
Vol 82 (13) ◽  
pp. 6772-6777 ◽  
Author(s):  
Zerina Kratovac ◽  
Cesar A. Virgen ◽  
Frederick Bibollet-Ruche ◽  
Beatrice H. Hahn ◽  
Paul D. Bieniasz ◽  
...  

ABSTRACT Mammalian cells express several factors that inhibit lentiviral infection and that have been under strong selective pressure. One of these factors, TRIM5, targets the capsid protein of incoming retrovirus particles and inhibits subsequent steps of the replication cycle. By substituting human immunodeficiency virus type 1 capsid, we were able to show that a set of divergent primate lentivirus capsids was generally not susceptible to restriction by TRIM5 proteins from higher primates. TRIM5α proteins from other primates exhibited distinct restriction specificities for primate lentivirus capsids. Finally, we identified novel primate lentiviral capsids that are targeted by TRIMCyp proteins.


2009 ◽  
Vol 90 (5) ◽  
pp. 1141-1147 ◽  
Author(s):  
Harriet C. T. Groom ◽  
Emma C. Anderson ◽  
John A. Dangerfield ◽  
Andrew M. L. Lever

Full-length human immunodeficiency virus type 1 (HIV-1) RNA acts as both mRNA, encoding Gag and Gag–Pol polyproteins, and genomic RNA. Translation of this RNA must be tightly controlled to allow sufficient protein synthesis prior to a switch to particle production. The viral protein Rev stimulates nuclear export of unspliced HIV-1 RNAs containing the Rev response element, but may also stimulate translation of these RNAs. We previously identified an additional Rev binding site in the 5′ untranslated region of the HIV-1 RNA. We show that Rev inhibits translation non-specifically at high concentrations and stimulates translation of HIV-1 RNAs at intermediate concentrations in vitro. Stimulation is dependent on the presence of the Rev binding site within the 5′ untranslated region and not on the Rev response element. In COS-1 cells, translation from an HIV-1 reporter is specifically increased by coexpression of Rev.


1998 ◽  
Vol 177 (6) ◽  
pp. 1549-1553 ◽  
Author(s):  
Richard T. D'Aquila ◽  
Lorraine Sutton ◽  
Anu Savara ◽  
Michael D. Hughes ◽  
Victoria A. Johnson

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