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Infection, Genetics and Evolution 11 (2011) 1449–1455
Molecular characterization of genotype G6 human rotavirus strains detectedin Italy from 1986 to 2009
Simona De Grazia a,*, Vito Martella b, Valentina Rotolo a, Floriana Bonura a, Jelle Matthijnssens c,Krisztian Banyai d, Max Ciarlet e, Giovanni M. Giammanco a
a Dipartimento di Scienze per la Promozione della Salute ‘‘G. D’Alessandro’’, Sezione di Microbiologia, Universita di Palermo, via del Vespro 133, 90127 Palermo, Italyb Dipartimento di Sanita Pubblica e Zootecnia, Universita di Bari, Italyc Laboratory of Clinical and Epidemiological Virology, Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgiumd Veterinary Medical Research Institute, Hungarian Academy of Sciences, Hungaria krt. 21, 1143 Budapest, Hungarye Novartis Vaccines & Diagnostics, Clinical Research Development, Cambridge, MA, USA
A R T I C L E I N F O
Article history:
Received 15 April 2011
Received in revised form 16 May 2011
Accepted 18 May 2011
Available online 26 May 2011
Keywords:
Rotavirus
Italy
Genotyping
G6
P[9]
P[14]
A B S T R A C T
Group A human rotavirus (HRV) strains with a bovine-like (G6) major outer capsid protein VP7 were first
detected in Palermo, Italy, in the late 1980s, and subsequently worldwide. During a 25-year rotavirus
surveillance period, additional HRV G6 strains, associated with either a P[9] or P[14] VP4 genotype, have
been detected sporadically, but repeatedly, in Palermo. Whether these G6 HRVs were transmitted to
humans directly from an animal reservoir or could have circulated at low prevalence in susceptible
individuals is uncertain. Upon sequence analyses of the VP7, VP4, VP6, NSP4 and NSP5 gene segments, all
the Italian HRV strains displayed a conserved genotype constellation, G6-P[9]/[14]-I2-E2-H3. Intra-
genotypic lineages and/or sub-lineages were observed among the various HRV strains, with some
lineage/sublineage combinations being retained over time. Interestingly, two epidemiologically
unrelated G6P[9] viruses, collected in the same rotavirus season, were found to have a clonal origin.
In conclusion, our results indicate not only diverse origin of animal derived G6 HRVs in Palermo but also
suggest human-to-human transmission of certain strains.
� 2011 Elsevier B.V. All rights reserved.
Contents lists available at ScienceDirect
Infection, Genetics and Evolution
jou r nal h o mep ag e: w ww .e ls evier . co m/lo c ate /m eeg id
1. Introduction
Group A rotaviruses (RVs) are important enteric pathogens inyoung children and livestock animals worldwide (Estes andKapikian, 2007). Complete RV virions are approximately 100 nmin diameter, icosahedral, triple-layered, and non-enveloped. Thegenome consists of 11 segments of double-stranded (ds)RNA (Estesand Kapikian, 2007). The outer protein layer is made up by twoproteins, the spike and viral attachment protein VP4 and the majorshell glycoprotein VP7, both of which form the basis for a binomialnomenclature. The VP4 is referred to as the P (protease-sensitive)antigen, and the VP7 as the G (glycosylated) antigen (Estes andKapikian, 2007). The majority (>90%) of medically importanthuman RV (HRV) strains belong to five major surface G and Pgenotype combinations, G1P[8], G2P[4], G3P[8], G4P[8], andG9P[8] (Ciarlet and Schodel, 2009; Matthijnssens et al., 2008b;Santos and Hoshino, 2005). Strains with unusual G/P genotypecombinations, mostly considered animal-like (zoonotic) RVstrains, are usually detected in a sporadic fashion in humans;
* Corresponding author. Tel.: +39 091 6553663; fax: +39 091 6553676.
E-mail address: [email protected] (S. De Grazia).
1567-1348/$ – see front matter � 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.meegid.2011.05.015
however, they can reach an epidemiological relevance in somegeographical settings, likely as the result of a process of adaptationvia accumulation of mutations or exchange of genomic segmentsvia reassortment (Martella et al., 2010). Several unusual andemerging HRVs (G8, G10, G11 and G12) are believed to have ananimal origin and to have been introduced into the humanpopulation through multiple events of interspecies transmissionfollowed by gene reassortment (Ciarlet et al., 2008; Martella et al.,2010; Matthijnssens et al., 2008c, 2010b; Santos and Hoshino,2005). In an attempt to standardize RV classification and to betterunderstand the evolutionary mechanisms behind the emergenceof novel RV strains, a new classification system based on anucleotide cut-off value for open reading frame (ORF) of each of the11 gene segments, has been proposed by the Rotavirus Classifica-tion Working Group (RCWG), assigning a one-letter code to each ofthe gene segments, and successive numbers for the differentgenotypes (Matthijnssens et al., 2008a,b). Upon full-lengthgenome sequence analyses a close evolutionary relationship hasbeen observed between human Wa-like and porcine RV strains,and between human DS-1-like and bovine RV strains, suggestingthat these two major human genogroups might have an animalorigin (Matthijnssens et al., 2008a). The increasing number ofsequence data of field strains continuously deposited to databases
S. De Grazia et al. / Infection, Genetics and Evolution 11 (2011) 1449–14551450
and the capability to produce laboratory strains through in vitro
cultivation and reassortment aided by newly established reversegenetics system require new standards and uniformity in rotavirusnomenclature and prompted the RCWG to propose a novelstandardized system to name RV strains according to the followingscheme: RV group/species of origin/country of identification/common name/year of identification/G- and P-type (Matthijnssenset al., in press).
Bovine-like HRV G6 strains, RVA/Human-tc/ITA/PA151/1987/G6P[9] and RVA/Human-tc/ITA/PA169/1988/G6P[14], respective-ly, were first identified in 1987 and 1988 from childrenhospitalised with acute gastroenteritis in Palermo, Italy (Gernaet al., 1992). Since then, G6P[9] and G6P[14] HRV strains have beendetected in children with gastroenteritis from several countries(Banyai et al., 2003, 2009a,b; Chandrahasen et al., 2010; Cooneyet al., 2001; Griffin et al., 2002; Martini et al., 2008; Matthijnssenset al., 2009a). In addition, G6 HRVs with other P types have beenidentified in several parts of Europe (G6P[4], G6P[6], G6P[8], andG6P[11]) (Iturriza-Gomara et al., 2010; Rahman et al., 2003). Todate complete genomes have been determined for a discretenumber of G6 HRVs, including six G6P[14] strains from Australia,Belgium, Hungary and Italy, one G6P[9] strains from the USA, and asingle probable human-animal reassortant G6P[6] strain fromBelgium (Heiman et al., 2008; Matthijnssens et al., 2008d, 2009a).A close genetic relatedness between human G6P[14] strains from aglobal collection and animal G6P[14] and G8P[14] viruses (fromruminants and ungulates) has been described, suggesting thatthese animals may act as reservoirs of G6 RV strains for humans(Banyai et al., 2009a,b, 2010; Matthijnssens et al., 2009a).
Uninterrupted surveillance for HRVs has been carried out inPalermo, Italy, for 25 years, thus providing a unique archivalcollection suitable for the study of epidemiologic trends andevolution of HRVs (Arista et al., 2006; De Grazia et al., 2007, 2009).During this surveillance activity, a total of seven G6 HRV strainshave been detected and found to posses either a P[9] or P[14] VP4genotype specificity. In order to gather information on the geneticconstellation of HRV G6 strains, and to investigate the geneticrelationships between the HRV G6 strains and other human andanimal RVs, the sequence of the VP7, VP4, VP6, NSP4 and NSP5genes was determined.
2. Materials and methods
The seven Italian G6 HRV strains were detected over a 15 yearstime span from 1987 to 2003. They were collected in November1987 (RVA/Human-tc/ITA/PA151/1987/G6P[9]), February 1988(RVA/Human-tc/ITA/PA169/1988/G6P[14]), January 1989 (RVA/Human-wt/ITA/PA5/1989/G6P[14]), November 1993 (RVA/Hu-man-wt/ITA/PA27-GV1/1993/G6P[9]), May 2002 (RVA/Human-wt/ITA/PA77/2002/G6P[14]) and November 2003 (RVA/Human-wt/ITA/PA17/2003/G6P[9] and RVA/Human-wt/ITA/PA43/2003/G6P[9]). All the strains were detected in stool samples fromchildren <5 years of age, who were hospitalised with acutegastroenteritis. The PA151 and PA169 strains were successfullyadapted to growth in MA104 cell cultures according to previouslyreported procedures (Gerna et al., 1992). The G6 typing wasperformed by EIA using type 1-, 2-, 3-, 4-, 6-, and 9-specificneutralizing monoclonal antibodies reactive with viral protein VP7or by RT-PCR for VP7-genotyping (Arista et al., 1990; Gouvea et al.,1990).
For this study the VP7, VP4, VP6, NSP4 and NSP5 genes of HRVstrains PA5-89, PA27-GV1-93, PA77-02, PA17-03 and PA43-03were amplified by RT-PCR (Gentsch et al., 1992; Gouvea et al.,1990; Iturriza-Gomara et al., 2002, 2004; Lee et al., 2000; Mohanand Atreya, 2001). The PCR amplicons generated were used toobtain partial gene sequences whose length varied from 715 to 843
nucleotides (nt) for VP4, from 232 to 247 nt for VP6, from 950 to1026 nt for VP7, from 631 to 722 nt for NSP4 and from 480 to588 nt for NSP5. Sequence alignment was performed usingCLUSTAL W (Thompson et al., 1994) and phylogenetic analysiswas carried out using the software MEGA 4.0 (Kumar et al., 2004).For the purpose of comparison and completeness, the sequences ofthe prototype G6 HRV strains PA151-87 and PA169-88 wereretrieved from GenBank (Gerna et al., 1994; Matthijnssens et al.,2009a; Nakagomi et al., 1993), with exception of the VP6 and NSP5gene sequences of strain PA151-87, which were determined in thisstudy. The accession numbers of the nucleotide (nt) sequencesobtained in this study are as follows: JF793931–JF793936 (VP6),JF793942–JF793946 (VP7), JF793937–JF793941 (VP8*), EU659855,JF793926–JF793930 (NSP4) and EU659852, JF793921–JF793925(NSP5) for the Italian HRV G6 strains, respectively.
3. Results and discussion
During a 25-years uninterrupted surveillance for HRVsconducted in Palermo, Italy, a total of seven G6 strains wereidentified. The Italian G6 HRV strains displayed a conservedgenomic constellation, G6-P[9]/P[14]-I2-E2-H3, differing only inthe VP4-coding gene. However, upon phylogenetic analysis, a morecomplex picture emerged. For VP7, the strains belonging togenotype G6 have been divided into eight (I–VIII) major lineages(Fig. 1a) based on this and previous studies (Chandrahasen et al.,2010; Rahman et al., 2003). The Italian G6P[9] HRV strainsclustered in G6-lineage I together with HRV strains isolated in USA(RVA/Human-tc/USA/Se584/1998/G6P[9]), Belgium (RVA/Human-wt/BEL/B1711/2002/G6P[6]), Hungary (RVA/Human-wt/HUN/Hun8/1998/G6P[9]) and France (RVA/Human-xx/FRA/R353/XXXX/G6P[6]), while the HRV G6P[14] strains segregated in G6-lineage II together with other HRV strains isolated in Italy (RVA/Human-tc/ITA/111-05-27/2005/G6P[14]), Australia (RVA/Human-tc/AUS/MG6/1993/G6P[14], RVA/Human-wt/AUS/SG6.01/1997/G6P[14], RVA/Human-wt/AUS/ASG6.02/1997/G6P[14]), Belgium(RVA/Human-wt/BEL/B10925/1997/G6P[14]) and Hungary (RVA/Human-wt/HUN/BP1879/2003/G6P[14]) and with animal RVAsidentified in South Africa (RVA/Goat-tc/ZAF/Cap455/XXXX/G6P[14] and RVA/antilope-wt/ZAF/RC-18/2008/G6P[14]). A num-ber of sub-lineages within G6 lineages I and II could be furtherdiscriminated (Ia to Id and IIa to IIe) (Fig. 1a). Most bovine RVs,including the G6-component of RotaTeq (RVA/Vaccine/RotaTeq-WI79-4/1992/G6P1A[8]), clustered in lineage IV, showing only80.9–84.9% nucleotide identity to the Italian HRV G6 strains.
By analysis of the VP8* portion of VP4, the Italian G6P[9] HRVsclustered together with feline, human AU-1-like, and humanG6P[9] RV strains detected in Hungary, Israel, Japan, Italy, France,Russia and USA (Fig. 1b). The Italian G6P[14] HRV strains PA5-89and PA77-02 clustered together with the prototype HRV G6P[14]strain PA169-88, and with G6/G8/G10 HRV and ungulate RV strainsfrom various parts of the world, including the human strains 111-05-27 (Italy), B10925 (Belgium), Hun5 (Hungary), EGY3399(Egypt) PR-1300-04 (Italy), A64 (England), MG6 and WAG8.1(Australia), the ovine strains OVR762 (Spain) and Cap455 (SouthAfrica), and the lama guanaco strain Chubut (Argentina), thebovine strain RUBV3 (India), and the antelope strain RC-18-08(South Africa). Five discrete lineages (a–e) were observed amongP[9] strains and nine lineages (a–i) were identified among P[14]viruses.
The I-genotypes (VP6), E-genotypes (NSP4) and H-genotype(NSP5) were also investigated, revealing that all the G6P[9] andG6P[14] Italian HRV strains belonged to the I2, E2 and H3genotypes. The VP6 genotype I2 strains were further classified into5 lineages (Fig. 1c), the NSP4 genotype E2 strains into 7 lineages(Fig. 1d), and the NSP5 genotype H3 strains into 7 lineages (Fig. 1e).
Fig. 1. Phylogenetic analysis of nucleotide sequences of the VP7 (a), VP4 (b), VP6 (c), NSP4 (d) and NSP5 (e) genes. Filled triangles indicate G6P[14] strains from this study;
open triangles G6P[14] strains from previous studies; filled circles G6P[9] strains from this study and open circles G6P[9] strains from previous studies. Rotavirus
nomenclature has been used according to the Rotavirus Classification Working Group (RCWG) (Matthijnssens et al., in press). Bootstrap values above 70%, estimated with
1000 pseudoreplicate data sets, are indicated at each node.
S. De Grazia et al. / Infection, Genetics and Evolution 11 (2011) 1449–1455 1451
Table 1Genetic constellation of seven potential zoonotic human strains detected in Palermo, Italy.
Sample ID VP7-VP4-VP6-
NSP4-NSP5
genotype
The most closely related rotavirus strains to the individual Italian rotavirus strains (shown with GenBank accession numbers and % nt identity)
VP7 VP4 VP6 NSP4 NSP5
Human Animal Human Animal Human Animal Human Animal Human Animal
PA151-87 G6-P[9]-I2-
E2-H3
95%: B1711
(EF504087)
89%: Bo/KN-4
(D12710)
98%: PAI58-96
(GU296427)
98%: Fe/Cat2
(EU708959)
93%: PAI58-96
(GU296429)
91%: Gu/Chubut
(FJ347104)
97%: PA169
(EF554135)
92%: Bo/XJX-07/
Ch (EU828786)
97%: PAI58-96
(GU296419)
98%: Fe/Cat2
(EU708966)
PA169-88 G6-P[14]-I2-
E2-H3
99%: MG6
(U22011)
95%: Ov/Cap455
(AY128708)
88%: Bo/
RUBV319
97%: B10925-97
(EF554118)
94%: Bo/RUBV81
(EF200548)
99%: SI-R230-07
(GU584061)
98%: Bo/NCDV
(DQ870496)
98%: PAI58-96
(GU296417)
93%: Ov/OVR762
(EF554157)
98%: B10925
(EF554125)
98%: Bo/KJ19-2
(FJ206054)
PA5-89 G6-P[14]-I2-
E2-H3
98%: 111-05-27
(EF554142)
97%: An/RC18-08
(RC1818)
97%: A64
(EF672563)
94%: Ov/Caprine
(AY128709)
90% Guanaco
(FJ347103)
98%: B10925
(EF554119)
95%: An/RC18-08
(FJ495131)
99%: B10925-97
(EF554124)
98%: Ov/OVR762
(EF554157)
97%: B10925
(EF554125)
98%: Si/PTRV
(FJ422141)
PA27-GV1-93 G6-P[9]-I2-
E2-H3
96%: PA151
(L20881)
88%: Bo/KN-4
(D12710)
99%: Hun2
(AJ488137)
98%: PAH136/96
95%: Fe/Cat2
(EU708959)
95%: 111-05-27
(EF554141)
97%: Bo/FR/
DijonA282/07
(GU259607)
97%: PAI58-96
(GU296417)
PA169 (EF554135)
93%: Ov/OVR762
(EF554157)
92%: Fe/BA222
99%: PAI58-96
(GU296419)
97%: Fe/Cat2
(EU708966)
PA77-02 G6-P[14]-I2-
E2-H3
98%: 111-05-27
(EF554142)
94%: Ov/Cap455
(AY128708)
92%: B10925-97
(EF554118)
90%: Ov/OVR762
(EF554151)
97%: BP1819/03/
HUN (AM992580)
98%: Ov/Sheep/
Aragon/08
(FN675938)
97%: B10925-97
(EF554124)
98%: Ov/OVR762
(EF554157)
99%: 111-05-27
(EF554147)
99%: Ov/OVR762
(EF554158)
PA17-03 G6-P[9]-I2-
E2-H3
98%: Hun7
(AJ488134)
89%: Bo/KN-4
(D12710)
97%: Hun8
(AJ488142)
96%: Fe/BA222
(GU827409)
99%: BP1819/03/
HUN (AM992579)
98%: Fe/BA222
(GU827410)
97%: N.N.11825
(DQ270109)
94%: PAH136-96
99%: Fe/BA222
(GU827415)
97%: PAH136-96
(GU296418)
96%: Fe/BA222
(GU827416)
PA43-03 G6-P[9]-I2-
E2-H3
97%: B1711
(EF504087)
86%: Bo/KN-4
(D12710)
97%: Hun8
(AJ488142)
97%: Fe/BA222
(GU827409)
99%: BP1819/03/
HUN (AM992579)
99%: Fe/BA222
(GU827410)
98%: N.N.11825
(DQ270109)
95%: PAH136-96
99%: Fe/BA222
(GU827415)
97%: PAH136-96
(GU296418)
97%: Fe/BA222
(GU827416)
Bo = bovine, Ov = ovine, An = antilope, Gu = guanaco, Fe = feline, Si = simian.
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Detailed comparison of the Italian G6 HRV strains with a selectionof G6 RV strains of different origin is shown in Table 1. Bycomparing with sequences in the online databases using a BLASTsearch (http://www.ncbi.nlm.nih.gov/BLAST), the Italian G6 HRVstrains appeared closely related to HRV strains that were in mostcases regarded as zoonotic viruses, in all the analysed genomesegments, but mainly in the VP4, VP6 and VP7 genes. Interestingly,the Italian HRV G6P[9] strains of this study displayed closesimilarity, mostly in their NSP5 segment, with multi-reassortantG3P[9] RVs (PAH136 and PAI58) detected in Palermo in 1996.These G3P[9] strains seem to have originated by multiplesequential reassortment events involving human/feline-likeRVA/Human-tc/AU-1/1982/G3P[9], RVA/Cat-tc/AUS/Cat-2/1984/G3P[9]-like viruses and RVs from ruminants (De Grazia et al.,2010; Martella et al., 2010) or may alternatively be a distinct feline/canine genogroup (Martella et al., 2011).
Unlike other studies, in which G6P[9] HRV strains weredetected in older children (Banyai et al., 2009a; Griffin et al.,2002), in the present study, the G6P[9] and G6P[14] HRV strainswere all detected in infants and young children (less than 5 years ofage). The G6 HRV strains detected in Palermo had no apparentepidemiological relationships to each other. An exception to thiswas represented by 2 distinct infections caused by G6P[9] HRVstrains, which occurred in 2003 within 3 days. The two isolates,PA17-03 and PA43-03, were highly similar to each other, sharing�99.5% nt identity in all the five gene segments analysed,indicating a likely clonal origin (Table 2). Nosocomial transmissionwas ruled out since the stool samples were collected on the firstday following admission to the same hospital. Although there wasno apparent relation between the two cases, it is reasonable toassume that the two children might have been exposed to acommon virus source or that the G6P[9] HRV strain wastransmitted directly or indirectly among the two patients. Thesefindings may provide evidence of secondary human-to-humantransmission of G6 RV strains, and may constitute an exception toprevious observations (Banyai et al., 2009a; Matthijnssens et al.,2009a).
Two G6P[9] HRV strains, PA151-87 and PA27-GV1-93, detected6 years apart in Palermo were found to share not only the samegenotype constellation, but also the same phylogenetic lineage inthree out of five genomic segments analysed (Table 2). G6P[9] HRVstrains retaining the same constellation for 4 genes (VP4, VP6, VP7,and NSP4) over a 7-years time span were also described fromHungary (Banyai et al., 2009a). High genetic conservation of somegenome segments may suggest that these strains are able tosuccessfully infect and cause disease in a human host althoughthey are not transmitted at high efficiency.
Detection of genotype P[14] HRV strains has been described indifferent geographic areas (Iturriza-Gomara et al., 2009, 2010;
Table 2Partial genomic constellations of the G6P[9] and G6P[14] Italian human rotaviruses (HR
sublineage (as evidenced in the phylogenetic trees) are shown with different shades o
Italian G6P[9] HRV VP7 VP4
G6 P[9]
Lineage (sublineage) Lineage
PA151-87 I(d) c
PA27-GV1-93 I(c) b
PA17-03 I(a) d
PA43-03 I(a) d
Italian G6P[14] HRV G6 P[14]
Lineage (sublineage) Lineag
PA169-88 II(b) h
PA5-89 II(d) d
PA77-02 II(d) h
Matthijnssens et al., 2009a). Upon complete genome analysis, fiveHRV G6P[14] strains revealed closer genetic relatedness to ovineand antelope RV strains, suggesting repeated interspecies trans-mission from sheep or other ungulates to humans (Matthijnssenset al., 2009a). Despite their widespread geographic distribution,HRV P[14] strains display a remarkable overall-conserved geno-type constellation. In our study, the same genome make up wasretained in the three G6P[14] HRV strains detected over 14 years(Table 2). Moreover, two of these strains PA5-89 and PA77-02,collected 13 years apart, shared the same lineage/sublineage infour genomic segments. These findings reinforce the observationsthat defined genome constellations may be required for transmis-sion of G6P[14] HRVs from the animal reservoirs to humans.
4. Conclusions
In this study, we determined and characterized the genotypeconstellation of seven G6 HRV strains detected in the geographicarea where the HRV G6 prototypes were first detected. Two G6P[9]clones were identified in 2003, providing possible evidence forhuman-to-human transmission. The transmission may not be veryefficient, since similar viruses were not detected anymore in orafter 2003 in Palermo. Circulation in humans, even at low rates,may provide a good opportunity for animal-like RVs to reassortwith HRVs, generating novel strains that could, theoretically, bebetter adapted to the human host than most animal RVs. However,this has not been observed yet. Epidemiological surveillance forHRV G and P genotypes throughout the world has been used todefine appropriate vaccine formulations to prevent RV infectionsin paediatric populations. At present, G6 HRVs are consideredoccasional human pathogens, transmitted sporadically fromanimal sources. One of the two licensed and worldwide distributedrotavirus vaccines, the pentavalent rotavirus vaccine, RotaTeq1
(Merck & Co., Inc. Whitehouse Station, NJ), contains five human-bovine reassortant strains, each expressing a different VP7 or VP4rotavirus surface protein, on the backbone of the naturallyattenuated tissue culture-adapted parental bovine rotavirus strainWC3 (G6P7[5]) (Matthijnssens et al., 2010). The efficacy of thevaccines has been assessed in large clinical trials, indicating thatthey are generally well tolerated, immunogenic and highlyefficacious (Armah et al., 2010; Madhi et al., 2010; Ruiz-Palacioset al., 2006; Tate et al., 2010; Vesikari et al., 2006, 2010; Zamanet al., 2010).
In Italy, the two licensed rotavirus vaccines RotaTeq1 andRotarix1 (GlaxoSmithKline Biologicals, Rixensart, Belgium) havebeen available since 2006 and 2007, respectively. However,rotavirus vaccine coverage is limited, and in 2008, only <0.4% ofchildren between 12 and 24 months of age had received eitherrotavirus vaccine (Istituto Superiore di Sanita, 2009). The first
Vs) included in this study. Segments genetically related within the same lineage or
f grey, to underline common patterns.
VP6 NSP4 NSP5
I2 E2 H3
Lineage Lineage Lineage
b a a
b a a
e b b
e b b
I2 E2 H3
e Lineage Lineage Lineage
c a a
a c a
a c a
S. De Grazia et al. / Infection, Genetics and Evolution 11 (2011) 1449–14551454
encouraging data on the impact of RV vaccination on theprevalence of disease caused by RV infections are becomingavailable (Chang et al., 2009; Clark et al., 2009; Tate et al., 2009;Zeller et al., 2010). Also there is evidence that the vaccines providegood homotypic and, in general, good heterotypic protection. Forexample, the recombinant components of the G1–G4 and P1A[8]strains included in the vaccine (Matthijnssens et al., 2010) wereproved efficacious against circulating G1–G4 and P[8] strains eventhough they are not genetically closely related. Similarly, the VP7sequences of the G6 strains circulating in humans are not veryclosely related to that of the G6 backbone strain in RotaTeq1
(Ciarlet et al., 2002; Matthijnssens et al., 2010). However, the‘‘lineage independent’’ efficacy demonstrated for the common HRVstrains is encouraging and hopefully a similar level of efficacy willbe reached against G6 HRVs where these strains are of medicalimportance. Ultimately, a better understanding of vaccine efficacyagainst various zoonotic or animal-derived HRVs, including theHRV G6P[9] and G6P[14] strains, requires continuous surveillanceof HRV in the post rotavirus vaccine era.
Acknowledgements
J.M. is supported by an FWO (‘Fonds voor WetenschappelijkOnderzoek’) postdoctoral fellowship. K.B. was supported by theHungarian Scientific Research Fund (OTKA, PD76364).
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