Congenital cytomegalovirus (cCMV) is a leading cause of birth defects. The guinea pig is the only small cCMV animal model. Guinea pig cytomegalovirus (GPCMV) encodes similar glycoprotein complexes to human CMV (HCMV) including gB and the gH-based pentamer complex (PC). In HCMV, both gB and PC are neutralizing antibody antigens. The relevance of GPCMV PC for virus tropism and vaccine target remains controversial. A novel guinea pig placental amniotic sac epithelial (GPASE) cell-line did not express viral cell receptor platelet derived growth factor receptor alpha (PDGFRA) and resulted in requirement for the PC for GPCMV infection unless PDGFRA was ectopically expressed. High titer anti-gB sera from a GPCMV gB vaccine study was evaluated for GPCMV neutralizing capability on GPASE cells in comparison to convalescent sera from GPCMV(PC+) or GPCMV(PC-) infected animals. Anti-gB sera neutralized fibroblast infection but was less effective compared to anti-GPCMV(PC-), which had antibodies to gH/gL. However, both anti-GPCMV(PC-) and anti-gB sera similarly had reduced neutralizing capability on GPASE and renal epithelial cells in comparison to anti-GPCMV(PC+) sera, which had additional antibodies to PC. Overall, results demonstrate the importance of the PC for GPCMV tropism to various cell types that lack PDGFRA expression and the limited ability of anti-gB sera to neutralize GPCMV on non-fibroblast cells despite the essential nature of gB glycoprotein.
CannonMJ,
GriffithsPD,
AstonV,
RawlinsonWD.
Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?. Rev Med Virol2014; 24:291–307 [View Article][PubMed]
LilleriD,
FornaraC,
FurioneM,
ZavattoniM,
RevelloMG et al. Development of human Cytomegalovirus–Specific T cell immunity during primary infection of pregnant women and its correlation with virus transmission to the fetus. J Infect Dis2007; 195:1062–1070 [View Article]
LilleriD,
GernaG.
Maternal immune correlates of protection from human cytomegalovirus transmission to the fetus after primary infection in pregnancy. Rev Med Virol2017; 27:e1921 [View Article]
GriffithBP,
McCormickSR,
FongCK,
LavalleeJT,
LuciaHL et al. The placenta as a site of cytomegalovirus infection in guinea pigs. J Virol1985; 55:402–409 [View Article]
ColemanS,
HornigJ,
MadduxS,
ChoiKY,
McGregorA.
Viral glycoprotein complex formation, essential function and immunogenicity in the guinea pig model for cytomegalovirus. PLoS One2015; 10:e0135567 [View Article]
ColemanS,
ChoiKY,
McGregorA.
Cytomegalovirus UL128 homolog mutants that form a pentameric complex produce virus with impaired epithelial and trophoblast cell tropism and altered pathogenicity in the guinea pig. Virology2017; 509:205–221 [View Article]
MiuraT,
MakinoR,
YamadaK,
MatsuuraM,
OkumuraM et al. Differences in the effects of mutations in GP131, a guinea pig cytomegalovirus homologue of pentameric complex component UL130, on macrophage and epithelial cell infection. J Gen Virol2018; 99:1425–1431 [View Article]
KabanovaA,
MarcandalliJ,
ZhouT,
BianchiS,
BaxaU et al. Platelet-Derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer. Nat Microbiol2016; 1:16082 [View Article]
WuY,
PragerA,
BoosS,
ReschM,
BrizicI et al. Human cytomegalovirus glycoprotein complex gH/gL/gO uses PDGFR-α as a key for entry. PLoS Pathog2017; 13:e1006281 [View Article]
ChoiKY,
El-HamdiNS,
McGregorA.
Inclusion of the viral pentamer complex in a vaccine design greatly improves protection against congenital cytomegalovirus in the guinea pig model. J Virol2019; 93: [View Article]
Martinez-MartinN,
MarcandalliJ,
HuangCS,
ArthurCP,
PerottiM et al. An unbiased screen for human cytomegalovirus identifies neuropilin-2 as a central viral receptor. Cell2018; 174:e191158–1171 [View Article]
SchleissMR,
McGregorA,
ChoiKY,
DateSV,
CuiX et al. Analysis of the nucleotide sequence of the guinea pig cytomegalovirus (GPCMV) genome. Virol J2008; 5:139 [View Article]
XingZ,
McFarlandCT,
SallenaveJM,
IzzoA,
WangJ et al. Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis. PLoS One2009; 4:e5856 [View Article]
BrittWJ,
HarrisonC.
Identification of an abundant disulfide-linked complex of glycoproteins in the envelope of guinea pig cytomegalovirus. Virology1994; 201:294–302 [View Article]
HornigJ,
ChoiKY,
McGregorA.
The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting. Virology2017; 504:122–140 [View Article]
Choi KYAM.
A New Strain of Guinea Pig CMV Suggests a More Prudent Strategy for Evaluation of Interventions Against Congenital CMV. Abstract # B-OP-018. 6th International Congenital CMV Conference/ 16th International CMV/betaherpesvirus Workshop The Netherlands: Noordwijkerhout; 2017
TabataT,
PetittM,
Fang-HooverJ,
ZydekM,
PereiraL.
Persistent cytomegalovirus infection in amniotic membranes of the human placenta. Am J Pathol2016; 186:2970–2986 [View Article]
El-HamdiNS,
Choi KYAM.
Platelet-derived growth factor-alpha receptor (PDGFRA) is the cell receptor for guinea pig cytomegalovirus fibroblast infection but not for trophoblast or congenital disease. Abstract# W3-12. 38th Annual Meeting American Society for Virology MN USA: Minneapolis; 2019
SchleissMR,
BourneN,
StroupG,
BravoFJ,
JensenNJ et al. Protection against congenital cytomegalovirus infection and disease in guinea pigs, conferred by a purified recombinant glycoprotein B vaccine. J Infect Dis2004; 189:1374–1381 [View Article]
FeireAL,
KossH,
ComptonT.
Cellular integrins function as entry receptors for human cytomegalovirus via a highly conserved disintegrin-like domain. Proc Natl Acad Sci USA2004; 101:15470–15475 [View Article]
WussowF,
YueY,
MartinezJ,
DeereJD,
LongmateJ et al. A vaccine based on the rhesus cytomegalovirus UL128 complex induces broadly neutralizing antibodies in rhesus macaques. J Virol2013; 87:1322–1332 [View Article]
AbelK,
MartinezJ,
YueY,
LaceySF,
WangZ et al. Vaccine-Induced control of viral shedding following rhesus cytomegalovirus challenge in rhesus macaques. J Virol2011; 85:2878–2890 [View Article]
AlbieroE,
AmatiE,
BaumeisterE,
EinseleH,
GrigoleitGU et al. Heterogeneity of specific CD4+ and CD8+ T cells stimulated by CMV pp65 and IE1 antigens. J Immunother2016; 39:329–342 [View Article][PubMed]
SchleissMR,
ChoiKY,
AndersonJ,
MashJG,
WettendorffM et al. Glycoprotein B (gB) vaccines adjuvanted with AS01 or AS02 protect female guinea pigs against cytomegalovirus (CMV) viremia and offspring mortality in a CMV-challenge model. Vaccine2014; 32:2756–2762 [View Article]
SchleissMR,
BourneN,
BernsteinDI.
Preconception vaccination with a glycoprotein B (gB) DNA vaccine protects against cytomegalovirus (CMV) transmission in the guinea pig model of congenital CMV infection. J Infect Dis2003; 188:1868–1874 [View Article]
SwansonEC,
GillisP,
Hernandez-AlvaradoN,
Fernández-AlarcónC,
SchmitM et al. Comparison of monovalent glycoprotein B with bivalent gB/pp65 (gp83) vaccine for congenital cytomegalovirus infection in a guinea pig model: inclusion of gp83 reduces GB antibody response but both vaccine approaches provide equivalent protection against pup mortality. Vaccine2015; 33:4013–4018 [View Article][PubMed]