After infection and integration steps,HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced.These encode Env (gp120 and gp41) and auxiliary proteins Vif,Vpr and VpU.The same localization within t...After infection and integration steps,HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced.These encode Env (gp120 and gp41) and auxiliary proteins Vif,Vpr and VpU.The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-1 infection process begins when the gp120 subunit of the envelope glycoprotein complex interacts with its receptor(s) on the target cell.The V3 domain of gp120 is the major determinant of cellular co-receptor binding.According to phenotypic information of HIV-1 isolates,sequences from the VpU to V3 regions (119 in R5-and 120 X4-tropic viruses;one per patient) were analysed.The binomial correlation phi coefficient was used to assess covariation among VpU and gp120 V3 signatures.Subsequently,average linkage hierarchical agglomerative clustering was performed.Beyond the classical V3 signatures (R5-viruses:S11,E25D;X4-viruses:S11KR,E25KRQ),other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage.Several statistically significant associations between V3 and VpU mutations were also observed.The dendrogram showed two distinct large clusters:one associated with R5-tropic sequences (bootstrap=0.94),involving:(a) H13NP V3,E25D V3,S11 V3,T22A V3 and Q61H VpU,(b) E25A V3 and L12F VpU,(c) D44E VpU,R18Q V3 and D80N VpU ;and another associated with X4-tropic sequences (bootstrap=0.97),involving:(i) E25I V3 and V10A VpU,(ii) 0-1insV VpU,H13R V3,I46L VpU,I30M V3 and 60-62del VpU,(iii) S11KR V3 and E25KRQ V3.Some of these pairs of mutations were encoded always by one specific codon.These data indicate the possible VpU mutational patterns contributing to regulation of HIV-1 tropism.展开更多
文摘After infection and integration steps,HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced.These encode Env (gp120 and gp41) and auxiliary proteins Vif,Vpr and VpU.The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-1 infection process begins when the gp120 subunit of the envelope glycoprotein complex interacts with its receptor(s) on the target cell.The V3 domain of gp120 is the major determinant of cellular co-receptor binding.According to phenotypic information of HIV-1 isolates,sequences from the VpU to V3 regions (119 in R5-and 120 X4-tropic viruses;one per patient) were analysed.The binomial correlation phi coefficient was used to assess covariation among VpU and gp120 V3 signatures.Subsequently,average linkage hierarchical agglomerative clustering was performed.Beyond the classical V3 signatures (R5-viruses:S11,E25D;X4-viruses:S11KR,E25KRQ),other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage.Several statistically significant associations between V3 and VpU mutations were also observed.The dendrogram showed two distinct large clusters:one associated with R5-tropic sequences (bootstrap=0.94),involving:(a) H13NP V3,E25D V3,S11 V3,T22A V3 and Q61H VpU,(b) E25A V3 and L12F VpU,(c) D44E VpU,R18Q V3 and D80N VpU ;and another associated with X4-tropic sequences (bootstrap=0.97),involving:(i) E25I V3 and V10A VpU,(ii) 0-1insV VpU,H13R V3,I46L VpU,I30M V3 and 60-62del VpU,(iii) S11KR V3 and E25KRQ V3.Some of these pairs of mutations were encoded always by one specific codon.These data indicate the possible VpU mutational patterns contributing to regulation of HIV-1 tropism.
