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Short Communication |
1 Cetacean Conservation Medicine Group (CMED), CEPEC/Museo de Delfines, Waldspielplatz 11, 82319 Starnberg, Germany
2 Département de Virologie, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
3 Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
4 Nuclear Research Centre (SCK-CEN), 200 Boeretang, B-2400 Mol, Belgium
5 Asociación ProDelphinus, Pasaje Octavio Bernal 572-5, Lima 11, Peru
Correspondence
Marie-Françoise Van Bressem
marievanbressem{at}yahoo.co.uk
Gérard Orth
gorth{at}pasteur.fr
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ABSTRACT |
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The GenBank/EMBL/DDBJ accession nos of the sequences reported in this paper are AJ238373, AJ006300 and AJ006301.
Supplementary data are available with the online version of this paper.
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MAIN TEXT |
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TOPABSTRACTMAIN TEXTREFERENCES |
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; Münger et al., 2004). PVs cause benign hyperproliferative epithelial lesions of the skin and mucosa (warts, papillomas and condylomas). High-risk PVs may induce invasive carcinomas (Lowy & Howley, 2001). Over 200 different PV types have been found in human beings and animals. They have been classified into 18 genera identified by Greek letters according to phylogenetic criteria (de Villiers et al., 2004; ICTV, 2006).
Genital warts caused by PVs are common in Burmeister's porpoises (Phocoena spinipinnis) from Peru (Van Bressem et al., 1996; Cassonnet et al., 1998). Here we report on the detection of two PV sequences in genital tumours of two porpoises and on the cloning and characterization of Phocoena spinipinnis papillomavirus type 1 (PsPV-1), the first PV isolated in cetaceans and the first genital PV detected in mammals belonging to an order other than the Primates (Cassonnet et al., 1998). Methods are described in Supplementary Methods, available in JGV Online.
Seven genital warts were collected from four porpoises from Peru (Supplementary Table S1, available in JGV Online). Group-specific PV antigen was detected in a wart of porpoise JAS-44 using antibodies against disrupted virions of human papillomavirus (HPV) type 1.
Total DNA extracted as described previously (Kawashima et al., 1990) was analysed by PCR using primers located in the L1 open reading frame (ORF) (Kawashima et al., 1990; Ting & Manos, 1990; de Roda Husman et al., 1995). A 560 bp fragment amplified by the IPC primers was detected in the PV antigen-positive JAS-44 wart after Southern blot hybridization with HPV-11 and HPV-16 L1 probes (L1-11 and L1-16; Kawashima et al., 1990) (Fig. 1a row i). DNA fragments were amplified from this sample after a single-step PCR with GP5+/GP6+ primers (Fig. 1a row ii) or a nested PCR using MY11/MY09 primers for the first round and GP5+/GP6+primers for the second (data not shown). Direct sequencing of the GP5+/GP6+ amplicons after the single-step (Ps1; GenBank accession no. AJ006300
[GenBank]
) and nested PCRs (Ps2; accession no. AJ006301
[GenBank]
) disclosed a 106 and a 97 bp long ORF, respectively (without the primers). Ps1 and Ps2 shared 56.6 % identical nucleotides. Their deduced polypeptide sequences (35 and 32 aa, respectively) presented 40 % identical amino acids, including six highly conserved residues diagnostic of PV L1 proteins (Fig. 1b) (Chan et al., 1997). The Ps1 nucleotide sequence was more closely related to the L1 sequence of HPV-90 (59.6 %) and the Ps2 sequence to the L1 of the manatee papillomavirus, TmPV-1 (66.3 %). Both have a high percentage of sequence identity with bovine papillomavirus (BPV) type 3, a member of the genus Xipapillomavirus (Ps1, 57.4 %; Ps2, 67.6 %). Ps1 presented the highest percentages of amino acid identity with HPV-4 (50 %), HPV-102 (48 %) and Capra hircus PV-1 (47 %), while Ps2 had highest identities with Equus caballus PV-1 (62 %), Capra hircus PV-1 (55 %) and Tursiops truncatus papillomavirus type 2 (TtPV-2, 51 %), using the NCBI BLASTP server. Divergences between PVs infecting the same host are not uncommon. Canis familiaris PV-2 is more closely related to bovine xipapillomaviruses and human gammapapillomaviruses than to canine oral PV and Felis domesticus PV (lambdapapillomaviruses) (Yuan et al., 2007). Presence of PV sequences in wart DNA preparations was further examined using Ps1a/b and Ps2a/b primers and Ps1 and Ps2 probes. In addition to JAS-44, Ps1 sequences were detected in one out of four vaginal lesions from porpoise JAS-50 (Fig. 1a row iii) and Ps2 sequences in the three other JAS-50 specimens (Fig. 1a row iv). Ps1 sequences were found in the one-step GP5+/GP6+ PCR products (Fig. 1a rows v and vii) and Ps2 sequences in the MY11/MY09 PCR products (Fig. 1a rows vi and viii). Thus, GP5+/GP6+ and MY11/MY09 primers identified two putative, distantly related, genital Phocoena spinipinnis PV (PsPV) types. PV sequences were not detected in two other genital warts (Fig. 1a), probably because of insufficient amounts of DNA.
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ZAP II DNA at the EcoRI site and subcloned (Short et al., 1988; Longuet et al., 1996). No recombinant phage-containing Ps2 sequence was isolated. The complete nucleotide sequence of the PsPV-1 genome was determined (GenBank accession no. AJ238373
[GenBank]
). It consists of 7879 bp and has a G+C content of 46.4 mol%. The ORFs encoding the early proteins E1, E2, E4 and E6 and the late proteins L1 and L2 are located on the same DNA strand. E4 ORF is collinear to E2 and has no potential ATG start codon.
The URR located between the stop codon of L1 and the first ATG of E6 is 621 bp long (positions 7366–107). It contains five potential promoter sequences (TATAA, TATAT or TATATAT) at positions 7408, 7569, 7860, 10 and 58, and the putative late AATAAA polyadenylation signal at position 7538. Two consensus binding sites (BSs) for the viral E2 protein (ACC-N6-GGT; Androphy et al., 1987) are found at positions 7830 and 40, flanking an E1-BS (ATGATTGTTAACAATTAT) (Ustav et al., 1991) located at position 7874. PsPV-1 URR also contains possible BSs for transcription factors found in the URR of genital HPVs (O'Connor et al., 1995), i.e., GC-box binding protein (SP1; positions 7671, 7712, 7735, 7753, 45), activator protein 1 (AP1; positions 7368, 7738, 7803), nuclear factor 1 (NF1; position 7752), octamer-binding protein 1 (Oct-1; position 7489), Ying Yang 1 (YY1; position 7405) and CCAAT/enhancer-binding protein (C/EBP; positions 7377, 7426, 7475, 7616). Several potential regulatory signals were found downstream of the URR: potential promoter sequences (TATAA at positions 581, 786, 1548, 1836 and 6861; TATATA at positions 783, 4087, 5137 and 6066), E2-BSs (positions 1376, 2943 and 5201) and potential polyadenylation signals (AATAAA, position 3448; ATTAAA, position 4199).
The PsPV-1 genome organization displays several atypical features. No E7 ORF was found. This was confirmed by sequencing the PCR products obtained after amplification of the region encompassing the 3' end of E6 and the 5'end of E1 directly from JAS-44 and JAS-50 DNA preparations. An E7 ORF is also missing in two other cetacean PVs, TtPV-1 and TtPV-2 (Rector et al., 2006; Rehtanz et al., 2006). E7 proteins promote proliferation of the basal and parabasal cells of squamous epithelia and allow vegetative viral DNA replication in growth-arrested, terminally differentiating keratinocytes (Howley & Lowy, 2001). In high-risk HPVs, E7 proteins fulfil this function by binding to members of the retinoblastoma (Rb) tumour suppressor protein family (Oh et al., 2004). A Leu-X-Cys-X-Glu sequence (Leu-Lys-Cys-Thr-Glu), critical for Rb protein-binding by HPV E7 (Howley & Lowy, 2001), is present in a putative 26 aa long peptide encoded by a short ORF overlapping the 5' end of PsPV-1 E1. It could be a remnant of an ancestral PV E7 ORF (Terai et al., 2002).
PsPV-1 E6 ORF encodes a 211 aa protein, larger than that usually observed in PVs (about 150 aa) (Howley & Lowy, 2001). A large E6 protein (206 aa) was also found in TtPV-2 (Rehtanz et al., 2006). The sequence of the PsPV-1 E6 protein can be aligned with E6 proteins of human and animal PVs over a 128 aa region (Ile-9 to Cys-136). This region harbours two conserved zinc-finger motifs CXXC-X29-CXXC separated by 36 aa (Cys-27 to Cys-136), as well as other conserved residues, such as Leu-12, Leu-34, Leu-47, Glu-86, Arg-99, Glu-111 or Lys-112 (Van Ranst et al., 1992; Howley & Lowy, 2001). These motifs and residues play a crucial role in the structure and activities of HPV E6 proteins (Nominé et al., 2006). In high-risk genital HPVs, a phenylalanine residue (Phe-47 for HPV-16) is important for the recruitment of the p53 protein to the ubiquitin ligase E6AP and for its E6-mediated degradation (Nominé et al., 2006). This residue is not conserved in PsPV-1 (Thr-44) or TtPV-2 (Tyr-63). The 75 aa long carboxyl-terminal end of PsPV-1 E6 has a high content (34.6 %) of serine and threonine but no cysteine. It shows no significant similarity with any PV protein, except for a stretch of 28 aa (positions 167–194) that shares 32 % identical amino acids with TtPV-2 E6. In contrast to TtPV-2 (Rehtanz et al., 2006), the extreme carboxyl terminus of PsPV-1 E6 does not harbour a PSD-95/Disc-large/ZO-1 (PDZ) domain-binding motif X-S/T-X-V/L (where X represents any amino acid) found in E6 proteins of genital oncogenic HPVs (Kiyono et al., 1997). The interaction of the E6 oncoproteins with specific PDZ proteins leads them to proteolytic degradation and probably plays an important role in pathogenesis (Münger et al., 2004).
PsPV-1 lacks the bona fide E5 ORF present in the E2–L2 intergenic region of alphapapillomaviruses and deltapapillomaviruses. In contrast, TtPV-2 has an E5 ORF encoding a putative 103 aa long protein with a 52.4 % Ile+Leu+Val content. PsPV-1 also lacks the E8 ORF observed in gammapapillomaviruses, kappapapillomaviruses and mupapillomaviruses devoid of an E5 ORF (Bravo & Alonso, 2004; García-Vallvé et al., 2005; Nonnenmacher et al., 2006) and in xipapillomaviruses lacking an E6 ORF (Jackson et al., 1991). E5 and E8 ORFs encode highly hydrophobic proteins that share similar properties and are allegedly essential for wart formation (Orth, 2006). Two short ORFs, tentatively named E5a and E5b, overlap the 3' end of the PsPV-1 E2 ORF. They lack a start codon and have a coding capacity for polypeptides of 37 (E5a) and 34 (E5b) aa. According to the TMHMM 2.0 program (Krogh et al., 2001), E5b may contain an 18 aa helical trans-membrane domain (Val-7 to His-23). Whether spliced transcripts allow the expression of these ORFs remains to be determined.
Despite the absence of E5/E8 and E7 ORFs and the occurrence of an unusual E6 protein, PsPV-1 seems able to cause genital warts in porpoises. Two additional ORFs, E3 and L3, with a potential start codon and a coding capacity for 61 (E3) and 169 (L3) aa polypeptides, overlap E1 and L1, respectively (Supplementary Fig. S1, available in JGV Online). Seven ORFs with an ATG start codon and a coding potential for 68–173 aa long polypeptides were detected on the complementary DNA strand (Supplementary Fig. S1). TATA boxes were found 19–250 nt upstream of their first ATG and polyadenylation signals (AATAAA) at positions 2101 and 7022 in the 5'
3' orientation. No predictable function was found by bioinformatics analysis for these nine putative proteins. None of them showed any significant similarity with proteins encoded by other PVs, including putative proteins encoded by the ORFs overlapping E1 or L1 or located on the complementary strand of the TtPV-2 genome (P. Cassonnet, unpublished observation). Whether some of these ORFs encode proteins that may complement those that are missing remains to be determined.
We investigated sequence identities between PsPV-1 and the prototypes of major PV genera and species. The percentage identities determined after pairwise alignments of the E6, E1, E2, E4, L2 and L1 ORFs and proteins are shown in Table 1. The highest scores were noted for the E1 and L1 ORFs, as expected (Howley & Lowy, 2001). For the E6 and E1 ORFs, PsPV-1 showed the highest identity percentages with TtPV-2 (unnamed genus) and HPV-6 (Alphapapillomavirus). When only the 420 nt corresponding to the first 140 aa of the PsPV-1 E6 protein were considered, the identity percentages increased with HPV-6 and decreased with TtPV-2. The highest identity scores for L1 and L2 ORFs were obtained for HPV-5, BPV-3 and TtPV-2. The fact that PsPV-1 L1 shares only 55 % nucleotide identity with the most closely related L1 ORFs warrants its classification as the sole member of the genus Omikronpapillomavirus (de Villiers et al., 2004).
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). In the early region, PsPV-1 clusters in a monophyletic branch with TtPV-2 (Fig. 2a, b), with high bootstrap values (99 %) for the E1E2 tree, whereas BPV-3 is included in the PsPV-1/TtPV-2 branch in the L1L2 region (Fig. 2c). The different phylogenies of the early and late genes of PsPV-1 further confirm that PV evolution may not be monophyletic across all genes (García-Vallvé et al., 2005; Narechania et al., 2005; Bravo & Alonso, 2006; Gottschling et al., 2006). The close phylogenetic relatedness of PsPV-1 and TtPV-2 and common features of their genetic organization suggest that a common ancestor of the Delphinidae and Phocoenidae (suborder Odontoceti) was infected with an ancestral cetacean PV that co-evolved with its hosts. The presence of a bona fide E5 ORF in TtPV-2 and its absence in PsPV-1 suggest that either this gene was lost from the PsPV-1 genome, or it accessed the TtPV-2 genome after the separation of Delphinidae and Phocoenidae about 11–25 million years ago (Fordyce & Barnes, 1994; Waddell et al., 2000; Nikaido et al., 2001).
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) probably represents another PV infecting members of the Phocoenidae. The unusual features of PsPV-1, its association with genital warts and the existence of a putative second genital PsPV emphasize the need to further study cetacean PVs to obtain a deeper insight into PV gene history and mechanisms underlying PV diversification.
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ACKNOWLEDGEMENTS |
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REFERENCES |
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TOPABSTRACTMAIN TEXTREFERENCES |
|---|
Bravo, I. G. & Alonso, A. (2004). Mucosal human papillomaviruses encode four different E5 proteins whose chemistry and phylogeny correlate with malignant and benign growth. J Virol 78, 13613–13626.
Bravo, I. G. & Alonso, A. (2006). Phylogeny and evolution of papillomaviruses based on the E1 and E2 proteins. Virus Genes 34, 249–262.[Medline]
Cassonnet, P., Van Bressem, M.-F., Desaintes, C., Van Waerebeek, K. & Orth, G. (1998). Papillomaviruses cause genital warts in small cetaceans from Peru. The World Marine Mammal Science Conference, Monaco, January 1998.
Chan, S.-Y., Bernard, H.-U., Ratterree, M., Birkebak, T. A., Faras, A. J. & Ostrow, R. S. (1997). Genomic diversity and evolution of papillomaviruses in rhesus monkeys. J Virol 71, 4938–4943.[Abstract]
de Roda Husman, A.-M., Walboomers, J. M. M., van den Brule, A. J. C., Meijer, C. J. L. M. & Snijders, P. J. F. (1995). The use of general primers GP5 and GP6 elongated at their 3' ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 76, 1057–1062.
de Villiers, E.-M., Fauquet, C., Broker, T. R., Bernard, H.-U. & zur Hausen, H. (2004). Classification of papillomaviruses. Virology 324, 17–27.[CrossRef][Medline]
Fordyce, R. E. & Barnes, L. G. (1994). The evolutionary history of whales and dolphins. Annu Rev Earth Planet Sci 22, 419–455.[CrossRef]
García-Vallvé, S., Alonso, A. & Bravo, I. G. (2005). Papillomaviruses: different genes have different histories. Trends Microbiol 13, 514–521.[CrossRef][Medline]
Gottschling, M., Köhler, A., Stockfleth, E. & Nindl, I. (2006). Phylogenetic analysis of beta-papillomaviruses as inferred from nucleotide and amino acid sequence data. Mol Phylogenet Evol 42, 213–222.[CrossRef][Medline]
Howley, P. M. & Lowy, D. R. (2001). Papillomaviruses and their replication. In Fields Virology, 4th edn, vol. 2, pp. 2197–2230. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
ICTV (2006). Papillomaviridae. In ICTVdB – The Universal Virus Database, version 4. Edited by C. Büchen-Osmond. New York: Columbia University. http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/index.htm
Jackson, M. E., Pennie, W. D., McCaffery, R. E., Smith, K. T., Grindlay, G. J. & Campo, M. S. (1991). The B subgroup bovine papillomaviruses lack an identifiable E6 open reading frame. Mol Carcinog 4, 382–387.[Medline]
Kawashima, M., Favre, M., Obalek, S., Jablonska, S. & Orth, G. (1990). Premalignant lesions and cancers of the skin in the general population. Evaluation of the role of human papillomaviruses. J Invest Dermatol 95, 537–542.[CrossRef][Medline]
Kiyono, T., Hiraiwa, A., Fujita, M., Hayashi, Y., Akiyama, T. & Ishibashi, M. (1997). Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A 94, 11612–11616.
Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E. L. (2001). Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305, 567–580.[CrossRef][Medline]
Longuet, M., Beaudenon, S. & Orth, G. (1996). Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70, related to the potentially oncogenic HPV39. J Clin Microbiol 34, 738–744.[Abstract]
Lowy, D. R. & Howley, P. M. (2001). Papillomaviruses. In Fields Virology, 4th edn, vol. 2, pp. 2231–2264. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
Münger, K., Baldwin, A., Edwards, K. M., Hayakawa, H., Nguyen, C. L., Owens, M., Grace, M. & Huh, K. W. (2004). Mechanisms of human papillomavirus-induced oncogenesis. J Virol 78, 11451–11460.
Narechania, A., Chen, Z., DeSalle, R. & Burk, R. D. (2005). Phylogenetic incongruence among oncogenic genital Alpha human papillomaviruses. J Virol 79, 15503–15510.
Nikaido, M., Matsuno, F., Hamilton, H., Brownell, R., Jr, Cao, Y., Ding, W., Zuoyan, Z., Shedlock, A. M., Fordyce, N. & other authors (2001). Retroposon analysis of major cetacean lineages: the monophyly of toothed whales and the paraphyly of river dolphins. Proc Natl Acad Sci U S A 98, 7384–7389.
Nominé, Y., Masson, M., Charbonnier, S., Zanier, K., Ristriani, T., Deryckère, F., Sibler, A.-P., Desplancq, D., Atkinson, R. A. & other authors (2006). Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis. Mol Cell 21, 665–678.[CrossRef][Medline]
Nonnenmacher, M., Salmon, J., Jacob, Y., Orth, G. & Breitburd, F. (2006). Cottontail rabbit papillomavirus E8 protein is essential for wart formation and provides new insights into viral pathogenesis. J Virol 80, 4890–4900.
O'Connor, M., Shan, S.-Y. & Bernard, H.-U. (1995). Transcription factor binding sites in the long control region of genital HPVs. In Human Papillomaviruses 1995. A Compilation and Analysis of Nucleic Acid and Amino Acid Sequences, vol. 3, pp. 21–40. Edited by G. Myers, H. Delius, J. Icenogle, H.-U. Bernard, C. Baker, A. Halpern & C. Wheeler. Los Alamos, NM : Los Alamos National Laboratory.
Oh, S. T., Longworth, M. S. & Laimins, L. A. (2004). Roles of the E6 and E7 proteins in the life cycle of low-risk human papillomavirus type 11. J Virol 78, 2620–2626.
Orth, G. (2006). Genetics of epidermodysplasia verruciformis: insights into host defense against papillomaviruses. Semin Immunol 18, 362–374.[CrossRef][Medline]
Rector, A., Lacave, G., Mostmans, S., Van Doorslaer, K., Rehtanz, M., Salbany, A., Roque, L., Ghim, S.-J., Bennett Jenson, A. & other authors (2006). The genetic characterization of a novel close-to-root papillomavirus in a bottlenose dolphin: Tursiops truncatus papillomavirus type 1 (TtPV-1). Abstracts of the 34th European Association for Aquatic Mammals (EAAM) Conference, Riccione, Italy, 17–20 March 2006.
Rehtanz, M., Ghim, S. J., Rector, A., Van Ranst, M., Fair, P., Bossart, G. D. & Jenson, A. B. (2006). Isolation and characterization of the first American bottlenose dolphin papillomavirus: Tursiops truncatus papillomavirus type 2. J Gen Virol 87, 3559–3565.
Short, J. M., Fernandez, J. M., Sorge, J. A. & Huse, W. D. (1988). ZAP: a bacteriophage expression vector with in vivo excision properties. Nucleic Acids Res 16, 7583–7600.
Terai, M., DeSalle, R. & Burk, R. D. (2002). Lack of canonical E6 and E7 open reading frames in bird papillomaviruses: Fringilla coelebs papillomavirus and Psittacus erithracus timneh papillomavirus. J Virol 76, 10020–10023.
Ting, Y. & Manos, M. (1990). Detection and typing of genital human papillomaviruses. In PCR Protocols: A Guide to Methods and Applications, pp. 356–367. Edited by M. A. Innis, D. H. Gelfand, J. J. Sninsky & T. J.White. San Diego: Academic Press.
Ustav, M., Ustav, E., Szymansky, P. & Stenlund, A. (1991). Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1. EMBO J 10, 4321–4329.[Medline]
Van Bressem, M.-F., Van Waerebeek, K., Piérard, G. E. & Desaintes, C. (1996). Genital and lingual warts in small cetaceans from coastal Peru. Dis Aquat Organ 26, 1–10.
Van Bressem, M.-F., Kastelein, R. A., Flamant, P. & Orth, G. (1999). Cutaneous papillomavirus infection in a harbour porpoise (Phocoena phocoena) from the North Sea. Vet Rec 144, 592–593.
Van Ranst, M., Kaplan, J. B. & Burk, R. D. (1992). Phylogenetic classification of human papillomaviruses: correlation with clinical manifestations. J Gen Virol 73, 2653–2660.
Waddell, V. G., Milinkovitch, M. C., Bérubé, M. & Stanhope, M. J. (2000). Molecular phylogenetic examination of the Delphinoidea trichotomy: congruent evidence from three nuclear loci indicates that porpoises (Phocoenidae) share a more recent common ancestry with white whales (Monodontidae) than they do with true dolphins (Delphinidae). Mol Phylogenet Evol 15, 314–318.[CrossRef][Medline]
Yuan, H., Ghim, S., Newsome, J., Apolinario, T., Olcese, V., Martin, M., Delius, H., Felsburg, P., Jenson, B. & other authors (2007). An epidermotropic canine papillomavirus with malignant potential contains an E5 gene and establishes a unique genus. Virology 359, 28–36.[CrossRef][Medline]
Received 7 November 2006;
accepted 27 February 2007.
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