Specific VpU Codon Changes were Significantly associated with gp120 V3 Tropic Signatures in HIV-1 B-subtype

Salvatore Dimonte; Muhammed Babakir-Mina; Stefano Aquaro; Carlo-Federico Perno

doi:10.1007/s12250-012-3287-0

December 2012

Salvatore Dimonte, Muhammed Babakir-Mina, Stefano Aquaro and Carlo-Federico Perno. Specific VpU Codon Changes were Significantly associated with gp120 V3 Tropic Signatures in HIV-1 B-subtype[J]. Virologica Sinica, 2012, 27(6): 360-368. doi: 10.1007/s12250-012-3287-0

Citation: Salvatore Dimonte, Muhammed Babakir-Mina, Stefano Aquaro, Carlo-Federico Perno. Specific VpU Codon Changes were Significantly associated with gp120 V3 Tropic Signatures in HIV-1 B-subtype .VIROLOGICA SINICA, 2012, 27(6) : 360-368. http://dx.doi.org/10.1007/s12250-012-3287-0

Specific VpU Codon Changes were Significantly associated with gp120 V3 Tropic Signatures in HIV-1 B-subtype

cstr: 32224.14.s12250-012-3287-0

1.
Department of Experimental Medicine and Biochemistry, University of Rome “Tor Vergata”, Rome, Italy; 2Slemani Polytechnic University, Iraqi Kurdistan Region; 3Faculty of Pharmacy, University of Calabria, Cosenza, Italy; 4National Institute for Infectious Diseases “LSpallanzani,” Rome, Italy.

通讯作者： Salvatore Dimonte, salvatore.dimonte@gmail.com;
收稿日期： 2012-09-17
录用日期： 2012-10-24

摘要

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 gp120V3 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) H13NPV3, E25DV3, S11V3, T22AV3 and Q61HVpU, (b) E25AV3 and L12FVpU, (c) D44EVpU, R18QV3 and D80NVpU; and another associated with X4-tropic sequences (bootstrap=0.97), involving: (i) E25IV3 and V10AVpU, (ii) 0-1insVVpU, H13RV3, I46LVpU, I30MV3 and 60-62delVpU, (iii) S11KRV3 and E25KRQV3. 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.
- HIV
- , VpU
- , gp120 V3
- , mutations
- , tropism
- , cluster analysis

Specific VpU Codon Changes were Significantly associated with gp120 V3 Tropic Signatures in HIV-1 B-subtype

1.
Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome 00133, Italy
2.
Slemani Polytechnic University; Iraqi Kurdistan Region
3.
Faculty of Pharmacy, Nutritional and Health Sciences, University of Calabria, Arcavacata di Rende (CS) 87036, Italy
4.
National Institute for Infectious Diseases "L. Spallanzani", Rome 00149, Italy

Corresponding author: Salvatore Dimonte, salvatore.dimonte@gmail.com
Received Date: 17 September 2012
Accepted Date: 24 October 2012

Abstract

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 gp120V3 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) H13NPV3, E25DV3, S11V3, T22AV3 and Q61HVpU, (b) E25AV3 and L12FVpU, (c) D44EVpU, R18QV3 and D80NVpU; and another associated with X4-tropic sequences (bootstrap=0.97), involving: (i) E25IV3 and V10AVpU, (ii) 0-1insVVpU, H13RV3, I46LVpU, I30MV3 and 60-62delVpU, (iii) S11KRV3 and E25KRQV3. 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.
- HIV
- , VpU
- , gp120 V3
- , Mutations
- , Tropism
- , Cluster analysis

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