scholarly journals Convalescent Immunity to Guinea Pig Cytomegalovirus Induces Limited Cross Strain Protection against Re-Infection but High-Level Protection against Congenital Disease

2020 ◽  
Vol 21 (17) ◽  
pp. 5997
Author(s):  
K. Yeon Choi ◽  
Nadia S. El-Hamdi ◽  
Alistair McGregor
Keyword(s):  
Guinea Pig ◽  
Small Animal ◽  
Prototype Strain ◽  
Small Animal Model ◽  
Viral Glycoprotein ◽  
Congenital Cytomegalovirus ◽  
Virus Challenge ◽  
Guinea Pig Cytomegalovirus ◽  
High Level ◽  
Human Cmv

The guinea pig is the only small animal model for congenital cytomegalovirus (cCMV) but requires guinea pig cytomegalovirus (GPCMV). Current GPCMV research utilizes prototype strain 22122, which limits the translational impact of GPCMV as numerous human CMV strains exist and cCMV is possible in the setting of re-infection. A novel strain of GPCMV (TAMYC) exhibited differences to 22122 in various glycoproteins with GP74 (gO homolog) the most variable (25% difference). Antibody ELISAs for TAMYC-convalescent animals evoked similar immune response to viral glycoprotein complexes (gB, gH/gL, gM/gN, pentamer) and cell-mediated response to pp65 homolog (GP83). Convalescent sera from TAMYC-infected animals neutralized GPCMV infection on fibroblasts but was less effective on epithelial cells. TAMYC-convalescent animals were not protected from dissemination of heterogenous virus challenge (22122). However, in a cCMV protection study, TAMYC-convalescent animals challenged mid-pregnancy (22122) exhibited high-level protection against cCMV compared to seronegative animals with pup transmission reduced from 80% (control) to 12%. Overall, pre-existing immunity in guinea pigs provides limited ability to prevent GPCMV re-infection by a different viral strain but provides a high level of protection against cCMV in heterogenous strain challenge. This level of cross protection against cCMV should be a prerequisite of any CMV vaccine.

scholarly journals Inclusion of the Viral Pentamer Complex in a Vaccine Design Greatly Improves Protection against Congenital Cytomegalovirus in the Guinea Pig Model

2019 ◽  
Vol 93 (22) ◽  
Author(s):  
K. Yeon Choi ◽  
Nadia S. El-Hamdi ◽  
Alistair McGregor
Keyword(s):  
Guinea Pig ◽  
Small Animal ◽  
Congenital Infection ◽  
Wild Type Virus ◽  
Fibroblast Cells ◽  
Type Virus ◽  
Wild Type ◽  
Small Animal Model ◽  
Congenital Cytomegalovirus ◽  
Guinea Pig Cytomegalovirus

ABSTRACT A vaccine against congenital cytomegalovirus (cCMV) is a high priority. The guinea pig is a small-animal model for cCMV. A disabled infectious single-cycle (DISC) viral vaccine strain based on a guinea pig cytomegalovirus (GPCMV) capsid mutant was evaluated. A previous version of this vaccine did not express the gH/gL-based pentamer complex (PC) and failed to fully protect against cCMV. The PC is necessary for GPCMV epithelial cell/trophoblast tropism and congenital infection and is a potentially important neutralizing antigen. Here, we show that a second-generation PC-positive (PC+) DISC (DISCII) vaccine induces neutralizing antibodies to the PC and other glycoproteins and a cell-mediated response to pp65 (GP83). Additionally, a CRISPR/Cas9 strategy identified guinea pig platelet-derived growth factor receptor alpha (PDGFRA) to be the receptor for PC-independent infection of fibroblast cells. Importantly, PDGFRA was absent in epithelial and trophoblast cells, which were dependent upon the viral PC for infection. Virus neutralization by DISCII antibodies on epithelial and trophoblast cells was similar to that in sera from wild-type virus-infected animals and dependent in part on PC-specific antibodies. In contrast, sera from PC-negative virus-infected animals poorly neutralized virus on non-fibroblast cells. DISCII-vaccinated animals were protected against congenital infection, in contrast to a nonvaccinated group. The target organs of pups in the vaccine group were negative for wild-type virus, unlike those of pups in the control group, with GPCMV transmission being approximately 80%. Overall, the DISCII vaccine had 97% efficacy against cCMV. The complete protection provided by this PC+ DISC vaccine makes the possibility of the use of this approach against human cCMV attractive. IMPORTANCE Cytomegalovirus (CMV) is a leading cause of congenital disease in newborns, and an effective vaccine remains an elusive goal. The guinea pig is the only small-animal model for cCMV. Guinea pig cytomegalovirus (GPCMV) encodes a glycoprotein pentamer complex (PC) for entry into non-fibroblast cells, including placental trophoblasts, to enable cCMV. As with human cytomegalovirus (HCMV), GPCMV uses a specific cell receptor (PDGFRA) for fibroblast entry, but other receptors are required for non-fibroblast cells. A disabled infectious single-cycle (DISC) GPCMV vaccine strain induced an antibody immune response to the viral pentamer to enhance virus neutralization on non-fibroblast cells, and vaccinated animals were fully protected against cCMV. Inclusion of the PC as part of a vaccine design dramatically improved vaccine efficacy, and this finding underlines the importance of the immune response to the PC in contributing toward protection against cCMV. This vaccine represents an important milestone in the development of a vaccine against cCMV.

scholarly journals A trimeric capable gB CMV vaccine provides limited protection against a highly cell associated and epithelial tropic strain of cytomegalovirus in guinea pigs

2021 ◽  
Vol 102 (3) ◽  
Author(s):  
K. Yeon Choi ◽  
Nadia S. El-Hamdi ◽  
Alistair McGregor
Keyword(s):  
Vaccine Candidate ◽  
Secondary Infection ◽  
Small Animal ◽  
Cell Types ◽  
Prototype Strain ◽  
Congenital Cytomegalovirus ◽  
Minimal Impact ◽  
Numerous Cell ◽  
Guinea Pig Cytomegalovirus ◽  
Multiple Strains

Multiple strains of human cytomegalovirus (HCMV) can cause congenital cytomegalovirus (cCMV) by primary or secondary infection. The viral gB glycoprotein is a leading vaccine candidate, essential for infection of all cell-types, and immunodominant antibody target. Guinea pig cytomegalovirus (GPCMV) is the only small animal model for cCMV. Various gB vaccines have shown efficacy but studies have utilized truncated gB and protection against prototype strain 22122 with preferential tropism to fibroblasts despite encoding a gH-based pentamer complex for non-fibroblast infection. A highly cell-associated novel strain of GPCMV (TAMYC) with 99 % identity in gB sequence to 22122 exhibited preferred tropism to epithelial cells. An adenovirus vaccine encoding full-length gB (AdgB) was highly immunogenic and partially protected against 22122 strain challenge in vaccinated animals but not when challenged with TAMYC strain. GPCMV studies with AdgB vaccine sera on numerous cell-types demonstrated impaired neutralization (NA50) compared to fibroblasts. GPCMV-convalescent sera including pentamer complex antibodies increased virus neutralization on non-fibroblasts and anti-gB depletion from GPCMV-convalescent sera had minimal impact on epithelial cell neutralization. GPCMV(PC+) 22122-convalescent animals challenged with TAMYC exhibited higher protection compared to AdgB vaccine. Overall, results suggest that antibody response to both gB and PC are important components of a GPCMV vaccine.

The pre-term guinea-pig: a model for the study of neonatal lung disease

1991 ◽  
Vol 81 (3) ◽  
pp. 439-446 ◽  
Author(s):  
F. J. Kelly ◽  
G. I. Town ◽  
G. J. Phillips ◽  
S. T. Holgate ◽  
W. R. Roche ◽  
...  
Keyword(s):  
Animal Model ◽  
Lung Injury ◽  
Guinea Pig ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Bronchoalveolar Lavage Fluid ◽  
Small Animal ◽  
Lavage Fluid ◽  
Small Animal Model ◽  
Neonatal Lung

1. Research into the pathogenesis of acute and chronic neonatal lung disease has been hampered by the lack of a suitable small-animal model of prematurity. We describe such a model that has been developed and validated in the guinea-pig. 2. Pre-term guinea-pigs delivered by Caesarian section at 65 days gestation (normal gestation 68 days) exhibited transient respiratory distress. The survival of pre-term animals was lower than that of term animals after exposure to 95% O2 (pre-term 42% versus term 79% at 96 h, P < 0.05). 3. Pulmonary histology in pre-term animals exposed to both 21% O2 and 95% O2 revealed evidence of acute lung injury with atelectasis, pulmonary oedema, fibrin deposition and inflammatory cell infiltration. No evidence of lung injury was observed in term animals exposed to 21% O2, whereas those exposed to 95% O2 showed a similar, but less pronounced, injury to that seen in preterm pups. 4. The protein concentration in bronchoalveolar lavage fluid was similar in pre-term and term animals exposed to 95% O2, but neutrophil numbers in bronchoalveolar lavage fluid tended to be greater in preterm pups. 5. Elastase-like activity, measured against succinyl-1-trialanine p-nitroanilide, was higher in bronchoalveolar lavage fluid from control pre-term animals compared with that from control term animals. Exposure to 95% O2 increased the elastase-like activity significantly in both groups. The majority of the elastase-like activity was EDTA-sensitive and thus is possibly due to metallo-elastase. Fractionation of bronchoalveolar lavage fluid indicated that the elastase-like activity was associated with a high-molecular-mass complex. Lipase treatment reduced the activity of this fraction and generated a new 40 kDa fraction. 6. We conclude that the pre-term guinea-pig is more susceptible than the term animal to lung injury after O2 exposure and thus represents a appropriate small-animal model in which to investigate the pathogenesis of acute and chronic lung injury in the pre-term infant.

scholarly journals A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

2016 ◽  
Vol 90 (17) ◽  
pp. 7902-7919 ◽  
Author(s):  
K. Yeon Choi ◽  
Matthew Root ◽  
Alistair McGregor
Keyword(s):  
Guinea Pig ◽  
Small Animal ◽  
Congenital Infection ◽  
T Cell Response ◽  
Control Group ◽  
Cmv Infection ◽  
Vaccine Strategy ◽  
Congenital Cmv Infection ◽  
Guinea Pig Cytomegalovirus ◽  
Congenital Cmv

ABSTRACTCongenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In thisdisabledinfectioussingle-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (theUL85homologGP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (105PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P= 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy.IMPORTANCECongenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. Thisdisabledinfectioussingle-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection.

scholarly journals Development and Characterization of a Guinea Pig-Adapted Sudan Virus

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Small Animal ◽  
Disease Outbreak ◽  
Small Animal Model ◽  
Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

scholarly journals Pathogenetical Characterization of MHV-76: a Spontaneous 9.5-Kilobase-Deletion Mutant of Murine Lymphotropic Gammaherpesvirus 68

2008 ◽  
Vol 77 (2) ◽  
pp. 231-237 ◽  
Author(s):  
A. Chalupková ◽  
M. Hricová ◽  
Z. Hrabovská ◽  
J. Mistríková
Keyword(s):  
Deletion Mutant ◽  
Infectious Virus ◽  
Chronic Phase ◽  
Small Animal ◽  
Mammary Glands ◽  
Prototype Strain ◽  
Peritoneal Macrophages ◽  
Small Animal Model ◽  
Gammaherpesvirus 68

Murid gammaherpesvirus 4 (MuHV-4) provides a small animal model for the study of animal gammaherpesviruses. MHV-76 is a spontaneous deletion mutant as compared to the prototype strain of MuHV-4 (MHV-68). The MHV-76 genome lacks at least 12 ORFs at the 5'-end including the M1, M2, M3 and M4 genes and the eight viral t-RNA-like genes. During 27 months of experimental infection of BALB/c mice we followed their pathogenesis, immunology and oncogenic properties. After intranasal infection with MHV-76, the infectious virus was detected in the blood, thymus, lungs, heart, liver, spleen, bone marrow, peritoneal macrophages, lymph nodes, kidneys, mammary glands, brain and small intestine. The acute phase of infection was attenuated, but the chronic phase of infection was accompanied with long persistence of virus not only in the lymphatic, but in the neural and glandular tissue, as well. In comparison with the prototype strain, splenomegaly and lymphocytosis was very low. Surprisingly, during 27 months the BALB/c mice infected with MHV-76 did not develop lymphoproliferative disorders like infectious mononucleosis, leukaemia or lymphomas. We hypothesize that the M4 gene, present in all oncogenic MHV isolates, might be related (directly or indirectly) to their transforming properties.

scholarly journals Molecular, Biological, and In Vivo Characterization of the Guinea Pig Cytomegalovirus (CMV) Homologs of the Human CMV Matrix Proteins pp71 (UL82) and pp65 (UL83)

2004 ◽  
Vol 78 (18) ◽  
pp. 9872-9889 ◽  
Author(s):  
Alistair McGregor ◽  
Fenyong Liu ◽  
Mark R. Schleiss
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Matrix Proteins ◽  
Wild Type ◽  
Viral Dna ◽  
Guinea Pig Cytomegalovirus ◽  
Human Cmv ◽  
Hsv 1

ABSTRACT We recently identified the genes encoding the guinea pig cytomegalovirus (GPCMV) homologs of the upper and lower matrix proteins of human CMV, pp71 (UL82) and pp65 (UL83), which we designated GP82 and GP83, respectively. Transient-expression studies with a GP82 plasmid demonstrated that the encoded protein targets the nucleus and that the infectivity and plaquing efficiency of cotransfected GPCMV viral DNA was enhanced by GP82. The transactivation function of GP82 was not limited to GPCMV, but was also observed for a heterologous virus, herpes simplex virus type 1 (HSV-1). This was confirmed by its ability to complement the growth of an HSV-1 VP16 transactivation-defective mutant virus in an HSV viral DNA cotransfection assay. Study of a GP82 “knockout” virus (and its attendant rescuant), generated on a GPCMV bacterial artificial chromosome construct, confirmed the essential nature of the gene. Conventional homologous recombination was used to generate a GP83 mutant to examine the role of GP83 in the viral life cycle. Comparison of the one-step growth kinetics of the GP83 mutant (vAM409) and wild-type GPCMV indicated that GP83 protein is not required for viral replication in tissue culture. The role of GP83 in vivo was examined by comparing the pathogenesis of wild-type GPCMV, vAM409, and a control virus, vAM403, in guinea pigs. The vAM409 mutant was significantly attenuated for dissemination in immunocompromised strain 2 guinea pigs, suggesting that the GP83 protein is essential for full pathogenicity in vivo.

scholarly journals Identification and functional analyses of a cell-death inhibitor encoded by guinea pig cytomegalovirus gp38.1 in cell culture and in animals

2020 ◽  
Vol 101 (12) ◽  
pp. 1270-1279
Author(s):  
Kazuma Noguchi ◽  
Ryuichi Majima ◽  
Keita Takahashi ◽  
Yoshihiko Iwase ◽  
Souichi Yamada ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Transient Transfection Assay ◽  
A Genome ◽  
Inhibitory Molecule ◽  
Guinea Pig Cytomegalovirus ◽  
Exon 1 ◽  
Induced Apoptosis ◽  
Human Cmv

Cytomegaloviruses (CMVs) employ an array of strategies designed to interfere with host defence responses against pathogens. Studies on such evasion mechanisms are important for understanding the pathogenesis of CMV diseases. Although guinea pig CMV (GPCMV) provides a useful animal model for congenital CMV infection, its evasion strategies are not fully elucidated. Here, we analysed a genome locus that may encode gene products for the GPCMV evasion mechanisms and found the following. (1) RACE analyses identified five transcripts in the GP38-gp38.4 locus, one of which was a spliced product encoding gp38.1. Similarities in the splicing pattern and gene position of gp38.1 to human CMV UL37 and its exon 1 encoding vMIA (viral mitochondria-localized inhibitor of apoptosis) suggest that the gp38.1 gene encodes an apoptosis inhibitor. (2) In a transient transfection assay, gp38.1 localized in the mitochondria and relocated BAX from the cytoplasm to the mitochondria, although its co-localization with BAK was not evident. Further, the expression of gp38.1 partially reduced staurosporine-induced apoptosis. (3) GPCMV defective in the gp38.1 ORF (Δ38.1) and the virus that rescues the defect (r38.1) were generated. Guinea pig fibroblast cells infected with Δ38.1 died earlier than r38.1-infected cells, which resulted in the lower yields of Δ38.1. (4) In animals, viral loads in the spleens of r38.1-infected guinea pigs were higher than those in the spleens of Δ38.1-infected animals. In conclusion, although GPCMV gp38.1 exerts a vMIA-like function, its inhibitory effect was not robust, suggesting the presence of additional inhibitory molecule(s), such as a BAK-specific inhibitor.

A small animal model study of perlite and fir bark dust on Guinea pig lungs

1983 ◽  
Vol 9 (3) ◽  
pp. 209-217 ◽  
Author(s):  
Robert F. McMichael ◽  
Joseph R. DiPalma ◽  
Robert Blumenstein ◽  
Peter S. Amenta ◽  
Allan P. Freedman ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Small Animal ◽  
Small Animal Model ◽  
Model Study ◽  
Animal Model Study

scholarly journals Guinea Pig Cytomegalovirus Protective T Cell Antigen GP83 Is a Functional pp65 Homolog for Innate Immune Evasion and Pentamer-Dependent Virus Tropism

2021 ◽  
Vol 95 (10) ◽  
Author(s):  
K. Yeon Choi ◽  
Nadia El-Hamdi ◽  
Julia Hornig ◽  
Alistair McGregor
Keyword(s):  
T Cell ◽  
Guinea Pig ◽  
Immune Evasion ◽  
Small Animal ◽  
Innate Immune ◽  
Clinical Strain ◽  
Virus Growth ◽  
Guinea Pig Cytomegalovirus ◽  
Sting Pathway ◽  
Innate Immune Evasion

ABSTRACT The guinea pig is the only small animal model for congenital cytomegalovirus (CMV) but requires species-specific guinea pig cytomegalovirus (GPCMV). Tegument protein GP83 is the presumed homolog of HCMV pp65, but gene duplication in the UL82-UL84 homolog locus in various animal CMVs made it unclear if GP83 was a functional homolog. A GP83 null deletion mutant GPCMV (GP83dPC+) generated in the backdrop of glycoprotein pentamer complex (PC)-positive virus, required for nonfibroblast infection, had normal growth kinetics on fibroblasts but was highly impaired on epithelial and trophoblast cells. GP83dPC+ virus was highly sensitive to type I interferon (IFN-I), suggesting that GP83 had an innate immune evasion function. GP83 interacted with cellular DNA sensors guinea pig IFI16 and cGAS, indicating a role in the cGAS/STING pathway. Ectopically expressed GP83 in trophoblast cells restored GP83dPC+ virus growth. Additionally, mutant virus growth was restored in epithelial cells by expression of bovine viral diarrhea virus (BVDV) Npro protein targeting IRF3 as part of the cGAS/STING pathway, or alternatively, by expression of the fibroblast cell receptor platelet-derived growth factor receptor alpha (PDGFRA). HCMV pp65 is a T cell target antigen, and a recombinant adenovirus encoding GP83 was evaluated as a vaccine. In GPCMV challenge studies, vaccinated animals had various levels of protection against wild-type virus, with a protective response against the 22122 prototype strain but little protection against a novel clinical strain of GPCMV (TAMYC), despite 100% identity in GP83 protein sequences. Overall, GP83 is a functional pp65 homolog with novel importance for epithelial cell infection, but a GP83 T cell response provides limited vaccine efficacy. IMPORTANCE Congenital CMV (cCMV) is a leading cause of cognitive impairment and deafness in newborns, and a vaccine is a high priority. The guinea pig is the only small animal model for cCMV but requires guinea pig cytomegalovirus (GPCMV). The translational impact of GPCMV research is potentially reduced if the virus does not encode functional HCMV homolog proteins. This study demonstrates that tegument protein GP83 (pp65 homolog) is involved in innate immune evasion and highly important for infection of nonfibroblast cells via the viral glycoprotein pentamer complex (PC)-dependent endocytic entry pathway. The PC pathway is highly significant for virus dissemination and disease in the host, including cCMV. A GP83 candidate adenovirus (Ad) vaccine strategy in animals induced a cell-mediated response but failed to provide cross-strain protection against a novel clinical strain of GPCMV. Results suggest that the pp65 antigen provides very limited efficacy as a stand-alone vaccine, especially in cross-strain protection.

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