Figure 3
From: Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors
Alignment of Pro and Pol amino acid sequences for XMRV and HIV-1. Alignments are shown for the protease (panel A), amino-terminal RT (panel B) and integrase catalytic core domain (CCD) sequences (panel C) of XMRVVP62 and HIV-1NL4-3 ([GenBank: NC_007815.1] and [GenBank: M19921], respectively). Numbering for XMRVVP62 is based on assigned amino acid numbers for the corresponding MoMLV peptides [GenBank: AF033811]. Alignments were generated using EMBOSS [62] with the following settings: gap-open = 10, gap extend = 0.5, algorithm = needle (global), scoring matrix = BLOSUM62. Amino acid identities between XMRVVP62 and HIV-1NL4-3 are shown with yellow boxes, conserved amino acid residues (BLOSUM62 score ≥1) are shown with grey boxes, and alignment gaps with are indicated with a dash (-). Catalytic active site residues are indicated with an asterisk (*). For RT, the initial EMBOSS alignment was manually adjusted to conform to a recent structural alignment of MoMLV and HIV-1 RTs [63]. Boundary boxes for conserved polymerase motifs A-D are shown as previously assigned [64]. Boundaries for motif F are shown as identified in alignments of viral RNA-dependent RNA polymerases [65]. The X at position five of XMRV protease indicates the location of a termination codon that, in MLV, is suppressed during translation of Gag-Pol-encoding RNA. Sites involved in antiretroviral drug resistance in HIV-1, as tabulated by the International AIDS Society-USA (for protease and RT) [40] or in the Stanford University HIV Drug Resistance Database (for integrase) [66] are indicated in bold, colored letters. The locations of primary PI, NRTI, and NNRTI resistance mutations, as well as changes associated with resistance to the integrase inhibitors raltegravir and elvitegravir, are shown in red. Sites involved in NNRTI resistance are shown in blue. Pound signs (#) indicate amino acid residues believed to be important for the positioning of strand transfer inhibitors, based on a recent structural analysis of prototype foamy virus integrase [51].