Pathogens, Vol. 11, Pages 1452: Viral Metagenomics Reveals a Putative Novel HPV Type in Anogenital Wart Tissues

A putative novel HPV type (HPV-JDFY01) was discovered from AGW, of which the complete circular genome is 7186 bp in length with a GC content of 36.6%. The details of the seven predicted ORFs are described as follows: Early proteins: E6 (nucleotide (nt) 1–420, 420 bp), E7 (nt 417–701, 285 bp), E1 (nt 688–2514, 1827 bp), E2 (nt 2447–3604, 1158 bp) and E4 (nt 3048–3374, 327 bp); Late proteins: L2 (nt 3606–5135, 1530 bp) and L1 (nt 5146–6699, 1554 bp); and a 487 bp long control region (LCR) is located at 6700 to 7186 of the genome between L1 and E6 (Figure 1). The putative E6 protein of HPV-JDFY01 contains two conserved zinc-finger domains, CxxC(x)29CxxC being located at nucleotide positions of 79–189 and 298–408, which are separated by 36 amino acids [28,29]. Three putative DZ binding domains (PTAL, nucleotide positions 16–27; LSLV, nucleotide positions 139–150 and ESLV, nucleotide positions 256–267) were also identified [30]. The putative E7, a downstream protein of E6, contains one zinc-finger domain (nucleotide positions 558–668), but no binding domain (LxCxE) for the conserved retinoblastoma tumor suppressor protein (pRB) [31]. As the largest protein of HPV-JDFY01, the putative E1 has one conserved ATP-binding site of the ATP-dependent DNA helicase with a consensus sequence (GPPDTGKS, nucleotide positions 1966–1989) and one typical bipartite nuclear localization signal (NLS) (KRK, nucleotide positions 919–927; KRRL, nucleotide positions 1009–1020). A leucine-rich nuclear export signal (NES) (LSPRLEAVKI, nucleotide positions 961–990) situates between the two clusters of NLS [32]. The putative E4 protein, with the highest proline content (12.8%), lies fully inside the E2. One highly conserved furin cleavage motif (RAKR, nucleotide positions 3620–3631) has been found at the N-terminal part of the L2 protein. In addition, a putative polyadenilation site (AATAAA, nucleotide positions 3695–3700) and a L2 transmembrane domain-like aa sequence (IIYLGGLGIGTGKGTG, nucleotide positions 3749–3796) are also observed [33]. NLS-like signals, which are used to direct HPV virions to import into the nucleus, are identified both at the C-terminal part of L2 protein (nucleotide positions 5099–5119) and in L1 of HPV-JDFY01 (nucleotide positions 6622–6696). The 487-bp LCR, also known as upstream regulatory region (URR), contains one putative polyadenilation site (AATAAA, nucleotide positions 6754–6759) and three palindromic E2-binding sites (ACC-AGTTCT-GGT, nucleotide positions 6914–6925; ACC-GATAAC-GGT, nucleotide positions 6955–6966 and ACC-AAGTGT-GGT, nucleotide positions 7135–7146) [34]. A TATA box (TATAAA, nucleotide positions 7150–7155) is located at the 31 nt upstream of E6’s first start codon. Most of the above-mentioned genetic characteristics could be examined in all other Gamma-8 species members. In view of the highest sequence identity of HPV-JDFY01 was only 74.2% with HPV-mSK_244 (MH777383), it needs to be confirmed as one putative novel HPV type by the current demarcation criteria of International Committee on the Taxonomy of Viruses (ICTV) [1,3].

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