scholarly journals Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

2016 ◽  
Vol 80 (3) ◽  
pp. 663-677 ◽  
Author(s):  
Thomas J. Gardner ◽  
Domenico Tortorella
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Humoral Immune Response ◽  
Cell Activation ◽  
Nk Cell ◽  
Cell Attachment ◽  
Immune Defense ◽  
Viral Glycoprotein ◽  
Humoral Immune

SUMMARYThe prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease.

scholarly journals Characterization of Lassa Virus Cell Entry and Neutralization with Lassa Virus Pseudoparticles

2009 ◽  
Vol 83 (7) ◽  
pp. 3228-3237 ◽  
Author(s):  
François-Loic Cosset ◽  
Philippe Marianneau ◽  
Geraldine Verney ◽  
Fabrice Gallais ◽  
Noel Tordo ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Cell Attachment ◽  
Low Ph ◽  
Cell Entry ◽  
Lassa Virus ◽  
Ph Optimum ◽  
Humoral Immune

ABSTRACT The cell entry and humoral immune response of the human pathogen Lassa virus (LV), a biosafety level 4 (BSL4) Old World arenavirus, are not well characterized. LV pseudoparticles (LVpp) are a surrogate model system that has been used to decipher factors and routes involved in LV cell entry under BSL2 conditions. Here, we describe LVpp, which are highly infectious, with titers approaching those obtained with pseudoparticles displaying G protein of vesicular stomatitis virus and their the use for the characterization of LV cell entry and neutralization. Upon cell attachment, LVpp utilize endocytic vesicles for cell entry as described for many pH-dependent viruses. However, the fusion of the LV glycoproteins is activated at unusually low pH values, with optimal fusion occurring between pH 4.5 and 3, a pH range at which fusion characteristics of viral glycoproteins have so far remained largely unexplored. Consistent with a shifted pH optimum for fusion activation, we found wild-type LV and LVpp to display a remarkable resistance to exposure to low pH. Finally, LVpp allow the fast and quantifiable detection of neutralizing antibodies in human and animal sera and will thus facilitate the study of the humoral immune response in LV infections.

scholarly journals Low-dose influenza vaccine Grippol Quadrivalent with adjuvant Polyoxidonium induces a T helper-2 mediated humoral immune response and increases NK cell activity

Vaccine ◽  
2020 ◽  
Vol 38 (42) ◽  
pp. 6645-6655
Author(s):  
Vladimir Talayev ◽  
Irina Zaichenko ◽  
Maria Svetlova ◽  
Alexei Matveichev ◽  
Olga Babaykina ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Vaccine ◽  
Humoral Immune Response ◽  
Low Dose ◽  
Nk Cell ◽  
Cell Activity ◽  
T Helper ◽  
Nk Cell Activity ◽  
T Helper 2 ◽  
Humoral Immune

scholarly journals Demonstration of the Genetic Stability and Temporal Expression of Select Members of the Lyme Disease Spirochete OspF Protein Family during Infection in Mice

2001 ◽  
Vol 69 (8) ◽  
pp. 4831-4838 ◽  
Author(s):  
John V. McDowell ◽  
Shian Ying Sung ◽  
Gregory Price ◽  
Richard T. Marconi
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Gene Family ◽  
Immune Evasion ◽  
Humoral Immune Response ◽  
Genetic Stability ◽  
Gene Families ◽  
Time Frame ◽  
Protein Family ◽  
Humoral Immune

ABSTRACT Infection with Lyme disease spirochetes can be chronic. This suggests that the spirochetes are capable of immune evasion. In a previous study we demonstrated that the ospE gene family, which is one of three gene families whose members are flanked at their 5′ end by the highly conserved upstream homology box (UHB) element, undergoes mutation and rearrangement during infection. This results in the generation of antigenically distinct variants that may contribute to immune evasion. In this study we have assessed the genetic stability of the UHB-flanked ospF gene family during infection in mice. Using postinfection clonal populations of Borrelia burgdorferi B31MI, PCR amplicons were generated for three members of the ospF gene family after a 3-month infection time frame. The amplicons were analyzed by single-nucleotide polymorphism pattern analysis and DNA sequencing. Members of the ospFgene family were found to be stable during infection, as no mutations or rearrangements were detected. An analysis of the humoral immune response to these proteins during infection revealed that the immune response to each is specific and that there is a delayed humoral immune response to some OspF protein family members. These analyses suggest that there is a temporal component to the expression of these genes during infection. In addition to a possible contribution to immune evasion, members of the OspF protein family may play specific roles at different stages of infection.

scholarly journals Glycoprotein H of human cytomegalovirus is a major antigen for the neutralizing humoral immune response

1996 ◽  
Vol 77 (7) ◽  
pp. 1537-1547 ◽  
Author(s):  
M. Urban ◽  
M. Klein ◽  
W. J. Britt ◽  
E. Hassfurther ◽  
M. Mach
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Humoral Immune Response ◽  
Humoral Immune ◽  
Glycoprotein H ◽  
Major Antigen

scholarly journals Humoral Immune Response to Human Cytomegalovirus in Patients Undergoing Percutaneous Transluminal Coronary Angioplasty

1999 ◽  
Vol 6 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Andreas Tiran ◽  
Rene A. Tio ◽  
Esther Oostenveld ◽  
Martin C. Harmsen ◽  
Beate Tiran ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Humoral Immune Response ◽  
Coronary Angioplasty ◽  
Odds Ratio ◽  
Hcmv Infection ◽  
Percutaneous Transluminal Coronary Angioplasty ◽  
Humoral Immune ◽  
Transluminal Coronary Angioplasty ◽  
Percutaneous Transluminal

ABSTRACT Possible causal relations between prior human cytomegalovirus (HCMV) infection and atherosclerosis and between HCMV reactivation and restenosis after coronary angioplasty have been suggested. We investigated patterns of antibodies directed to HCMV in 112 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and in a group of sex- and age-matched controls (blood donors without evidence of atherosclerosis). Levels of antibodies to HCMV were measured by enzyme-linked immunosorbent assay (ELISA) of serum samples drawn before and 5 weeks after PTCA. To further differentiate the humoral immune response, we specifically tested antibody reactivity towards four single HCMV proteins (IE2, p52, pp150, and pp65) by recombinant ELISAs. We found that 73% of PTCA patients and 69% of sex- and age-matched controls were seropositive for HCMV (odds ratio, 1.2 [not significant]). The corresponding odds ratios for matched pairs ranged in the recombinant ELISAs from 1.2 to 1.4. Patients had more often high titers of anti-HCMV antibodies (11 versus 4%; odds ratio = 3.3 [0.9 to 15.2]; P = 0.052) and high titers of anti-pp150 antibodies (13 versus 4%; odds ratio = 6.0 [1.3 to 38.8]; P = 0.008). Anti-HCMV immunoglobulin M antibodies were not detected in any patient. There was no evidence of acute HCMV reactivation after PTCA, since the titers of antibodies to the investigated recombinant proteins did not increase at 5 weeks after PTCA. Our results show a limited association between prior HCMV infection and coronary artery disease. We infer that positive anti-HCMV titers are not a major risk factor at the time of disease manifestation. However, this study cannot rule out a possible role of HCMV at earlier stages of the atherosclerotic process. Recombinant ELISAs provide a valuable tool for investigating the antiviral immune response.

Constitutive Expression of Human Cytomegalovirus (HCMV) Glycoprotein gpUL75 (gH) in Astrocytoma Cells: A Study of the Specific Humoral Immune Response

1999 ◽  
Vol 12 (3) ◽  
pp. 249-262 ◽  
Author(s):  
MARKO RESCHKE ◽  
MARIA GRAZIA REVELLO ◽  
ELENA PERCIVALLE ◽  
KLAUS RADSAK ◽  
MARIA PAOLA LANDINI
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Humoral Immune Response ◽  
Constitutive Expression ◽  
Humoral Immune ◽  
Astrocytoma Cells

scholarly journals MERS-CoV Spike Protein Vaccine and Inactivated Influenza Vaccine Formulated with Single Strand RNA Adjuvant Induce T-Cell Activation through Intranasal Immunization in Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 441
Author(s):  
Hye-Jung Kim ◽  
Hye Won Kwak ◽  
Kyung Won Kang ◽  
Yoo-Jin Bang ◽  
Yu-Sun Lee ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Influenza Vaccine ◽  
T Cell Activation ◽  
Humoral Immune Response ◽  
Cell Activation ◽  
Spike Protein ◽  
Intranasal Immunization ◽  
Humoral Immune ◽  
Inoculation Route

The effectiveness of vaccines is enhanced by adding adjuvants. Furthermore, the selection of an inoculation route depends on the type of adjuvant used and is important for achieving optimum vaccine efficacy. We investigated the immunological differences between two types of vaccines—spike protein from the Middle East respiratory syndrome virus and inactivated influenza virus vaccine, in combination with a single-stranded RNA adjuvant—administered through various routes (intramuscular, intradermal, and intranasal) to BALB/c mice. Intramuscular immunization with the RNA adjuvant-formulated spike protein elicited the highest humoral immune response, characterized by IgG1 and neutralizing antibody production. Although intranasal immunization did not elicit a humoral response, it showed extensive T-cell activation through large-scale induction of interferon-γ- and interleukin-2-secreting cells, as well as CD4+ T-cell activation in mouse splenocytes. Moreover, only intranasal immunization induced IgA production. When immunized with the inactivated influenza vaccine, administration of the RNA adjuvant via all routes led to protection after viral challenge, regardless of the presence of a vaccine-specific antibody. Therefore, the inoculation route should depend on the type of immune response needed; i.e., the intramuscular route is suitable for eliciting a humoral immune response, whereas the intranasal route is useful for T-cell activation and IgA induction.

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