scholarly journals The tegument protein ppUL25 of human cytomegalovirus (CMV) is a major target antigen for the anti-CMV antibody response

2001 ◽  
Vol 82 (2) ◽  
pp. 335-338 ◽  
Author(s):  
Tiziana Lazzarotto ◽  
Stefania Varani ◽  
Liliana Gabrielli ◽  
Sara Pignatelli ◽  
Maria Paola Landini

A viral protein of approximately 82 kDa is the only structural protein of human cytomegalovirus (CMV) that is strongly immunogenic during natural infection and the corresponding gene of which is still unknown. In this work, strong evidence is presented that this protein is the product of UL25.

2018 ◽  
Vol 92 (9) ◽  
Author(s):  
Gregor Maschkowitz ◽  
Sabine Gärtner ◽  
Heike Hofmann-Winkler ◽  
Helmut Fickenscher ◽  
Michael Winkler

ABSTRACTHuman cytomegalovirus (HCMV) is a widespread human pathogen that causes asymptomatic infection in healthy individuals but poses a serious threat to immunocompromised patients. During the late phase of HCMV infection, the viral capsid is transported to the cytoplasmic viral assembly center (cVAC), where it is enclosed by the tegument protein layer and the viral envelope. The cVAC consists of circularly arranged vesicles from thetrans-Golgi and endosomal networks. The HCMV gene UL35 encodes ppUL35 and its shorter form, ppUL35A. We have previously shown that the UL35 gene is involved in HCMV assembly, but it is unknown how UL35 proteins regulate viral assembly. Here we show that sorting nexin 5 (SNX5), a component of the retromer and part of the retrograde transport pathway, interacts with UL35 proteins. Expression of wild-type proteins but not mutants defective in SNX5 binding resulted in the cellular redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR), indicating that UL35 proteins bind and negatively regulate SNX5 to modulate cellular transport pathways. Furthermore, binding of UL35 proteins to SNX5 was required for efficient viral replication and for transport of the most abundant HCMV glycoprotein B (gB; gpUL55) to the cVAC. These results indicate that ppUL35 and ppUL35A control the localization of the essential gB through the regulation of a retrograde transport pathway. Thus, this work is the first to define a molecular interaction between a tegument protein and a vesicular transport factor to regulate glycoprotein localization.IMPORTANCEHuman cytomegalovirus is ubiquitously present in the healthy population, but reactivation or reinfection can cause serious, life-threatening infections in immunocompromised patients. For completion of its lytic cycle, human cytomegalovirus induces formation of an assembly center where mature virus particles are formed from multiple viral proteins. Viral glycoproteins use separate vesicular pathways for transport to the assembly center, which are incompletely understood. Our research identified a viral structural protein which affects the localization of one of the major glycoproteins. We could link this change in glycoprotein localization to an interaction of the structural protein with a cellular protein involved in regulation of vesicle transport. This increases our understanding of how the virus intersects into cellular regulatory pathways to enhance its own replication.


Vaccine ◽  
2011 ◽  
Vol 29 (48) ◽  
pp. 9075-9080 ◽  
Author(s):  
Dai Wang ◽  
Fengsheng Li ◽  
Daniel C. Freed ◽  
Adam C. Finnefrock ◽  
Aimin Tang ◽  
...  

1991 ◽  
Vol 164 (5) ◽  
pp. 835-842 ◽  
Author(s):  
L. Rasmussen ◽  
C. Matkin ◽  
R. Spaete ◽  
C. Pachl ◽  
T. C. Merigan

2009 ◽  
Vol 90 (8) ◽  
pp. 1951-1961 ◽  
Author(s):  
Christiane Burkhardt ◽  
Susanne Himmelein ◽  
William Britt ◽  
Thomas Winkler ◽  
Michael Mach

Human cytomegalovirus (HCMV) encodes several highly polymorphic envelope glycoproteins; however, the biological relevance of this polymorphism is unclear. Glycoprotein N (gN) is one member of this polymorphic protein family. Four major gN genotypes (gN1–4) have been identified. We have tested the hypothesis that the gN polymorphism represents a mechanism to evade a neutralizing antiviral antibody response. Four recombinant viruses that differed only in the expression of the gN genotype were constructed on the genetic background of HCMV strain AD169. Exchange of gN genotypes had a minor detectable influence on virus replication, gN expression and gN–gM complex formation. Randomly selected human sera were analysed for neutralizing activity against the recombinant viruses. Of these, 70 % showed no difference in neutralizing titre between the viruses, whereas 30 % showed strain-specific neutralization. Differences in 50 % neutralization titre reached >8-fold. Viruses expressing the gN4 genotype were neutralized significantly better than those expressing the other gN genotypes. Strain specificity, or lack thereof, could not be attributed to the presence or absence of anti-gN antibodies, as all sera contained antibodies reacting with gN (as determined by ELISA). Thus, polymorphism of gN could contribute to evasion of an efficient neutralizing-antibody response and facilitate reinfection in previously seropositive individuals.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1007
Author(s):  
Karin Stiasny ◽  
Agnes Leitner ◽  
Heidemarie Holzmann ◽  
Franz X. Heinz

Tick-borne encephalitis (TBE) has a substantial impact on human public health in many parts of Europe and Asia. Effective inactivated purified whole-virus vaccines are in widespread use in TBE-endemic countries. Nevertheless, vaccination breakthroughs (VBTs) with manifest clinical disease do occur, and their specific serodiagnosis was shown to be facilitated by the detection of antibodies to a non-structural protein (NS1) that is produced during virus replication. However, recent data have shown that NS1 is also present in the current inactivated vaccines, with the potential of inducing corresponding antibodies and obscuring a proper interpretation of NS1-antibody assays for diagnosing VBTs. In our study, we quantified anti-virion and anti-NS1 antibody responses after vaccination as well as after natural infection in TBE patients, both without and with a history of previous TBE vaccination (VBTs). We did not find significant levels of NS1-specific antibodies in serum samples from 48 vaccinees with a completed vaccination schedule. In contrast, all TBE patients mounted an anti-NS1 antibody response, irrespective of whether they were vaccinated or not. Neither the dynamics nor the extent of NS1-antibody formation differed significantly between the two cohorts, arguing against substantial NS1-specific priming and an anamnestic NS1-antibody response in VBTs.


2002 ◽  
Vol 83 (5) ◽  
pp. 1005-1012 ◽  
Author(s):  
P. Dal Monte ◽  
S. Pignatelli ◽  
N. Zini ◽  
N. M. Maraldi ◽  
E. Perret ◽  
...  

Human cytomegalovirus (HCMV) UL53 belongs to a family of conserved herpesvirus genes. In this work, the expression and localization of the UL53 gene product was analysed. Results obtained showed that pUL53 is a new structural protein. In infected human fibroblasts, pUL53 localizes in cytoplasmic perinuclear granular formations together with other structural viral proteins. In the nucleus, pUL53 forms patches at the nuclear periphery and co-localizes with lamin B at the internal nuclear membrane level. Immunoelectron microscopy studies have disclosed that nuclear pseudo-inclusions are labelled, whereas nucleocapsid formations within the intranuclear skein are negative. Furthermore, the mature virus particle maintains pUL53 at its tegumental level. These data suggest that pUL53 could be involved either in nucleocapsid maturation or in the egress of nucleocapsids from the nucleus to the cytoplasm through the nuclear membrane, a role compatible with the function hypothesized for UL31, its positional homologue in herpes simplex virus type 1.


2021 ◽  
Author(s):  
Sarah E Messiah ◽  
Frances A Brito ◽  
Harold W Kohl ◽  
Stacia M DeSantis ◽  
Melissa A Valerio-Shewmaker ◽  
...  

Background. Recent data suggest the SARS-CoV-2 Delta (B.1.617.2) variant is more transmissible among children compared to the Alpha (B.1.1.7) variant. The true incidence and longitudinal presence of antibody response to SARS-CoV-2 infection is not known, however. We provided estimates of antibody response using Texas Coronavirus Antibody REsponse Survey (Texas CARES) data, a prospective population-based seroprevalence project designed to assess antibody status over time among the general population throughout the state. Methods. In October 2020 Texas CARES began enrolling adults (aged 20-80 years) and children (aged 5-19 years). Participants were offered a series of three SARS-CoV-2 antibody tests over 6-8 months, or every 2-3 months that includes the immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test). Descriptive characteristics and COVID-19 infection-related symptom status was determined by questionnaire at the time of enrollment and prior to each successive blood draw. This analysis included participants ages 5-to-19 years old who have completed all three antibody assessments. Results. From our sample (n=159; mean age 12.5 years, SD 3.6), 96% of those with evidence of nucleocapsid antibodies at baseline assessment continued to have antibodies > six months later (mean 7.0 months, SD 0.97). There was no difference in the presence of antibodies by symptom status (asymptotic versus symptomatic) or severity (mild-moderate versus severe), sex, age group, or body mass index group (underweight, healthy weight, overweight, obesity) over the three antibody measurement timepoints. Conclusions. These results suggest that infection-induced antibodies persist and thus may provide some protection against future infection for at least half a year. 57.9% of the sample were negative for infection-induced antibodies at their third measurement point, suggesting a significant proportion of children have still not acquired natural infection.


2021 ◽  
Author(s):  
Massimo La Raja ◽  
Monia Pacenti ◽  
Ileana Grimaldi ◽  
Caterina Boldrin ◽  
Margherita Cattai ◽  
...  

From April 2020 through May 2021 in Padova Province 3395 COVID-19 recovered patients were recruited as potential convalescent plasma donors and tested for SARS-CoV-2 antibodies. Since January 2021 COVID-19 vaccination campaign began in Italy, the impact of vaccination on antibody levels and suspect vaccine breakthrough infections in these subjects were investigated. Post-vaccination anti-Sars-Cov-2 antibody level in 54 previously infected subjects had an exponential increase compared to pre-vaccination level regardless of the number of vaccine doses. However after 100 days from vaccination SARS-CoV-2 antibody level tends to decline. Post-vaccination primary infections were detected in 15 cases, with 3 possible breakthrough infections after a full vaccination course. In these cases, antibody response after infection was present but weaker than the one of subjects vaccinated after natural infection. A trend toward stronger antibody response was observed with increasing distance between natural infection and vaccination. Additionally, 2 cases of asymptomatic reinfections are also discussed.


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