Molecular Dissection of the Humoral Immune Response to Individual Varicella-Zoster Viral Proteins During Chickenpox, Quiescence, Reinfection, and Reactivation

Abstract

The sequence of antibody formation to molecularly defined varicella-zoster virus (VZV) proteins was examined during the course of chickenpox, quiescence, and subsequent VZV reactivation and reinfection. The first antibodies produced after primary VZV infection were to two virion envelope glycoproteins, gp66 and gp118 , and the nucleocapsid protein p155 . Within one to two months, antibodies to a greater array of viral proteins and glycoproteins were observed. Antibodies to the immunodominant viral proteins ( gp66 , gp118 , and p155 ) persisted for years after varicella and were, therefore, excellent markers of prior VZV infection. Subclinical VZV reinfection also was associated with transient rises in levels of the same polypeptide-specific antibodies as during primary disease. The immunoglobulin response to zoster appeared more rapidly than that to chickenpox or reinfection and was to the broadest complement of viral proteins, including the distinctive VZV polypeptide p32. These radioimmune-precipitation profiles could be subdivided into six different patterns characteristic of the following clinical states: acute- and convalescent-phase chickenpox, quiescence, acute- and convalescent-phase zoster, and postzoster quiescence.

Detection of Antibodies to Varicella-Zoster Virus Proteins in Sera from the Elderly

“…Sim ilar to young individuals [Weigle and Grose, 1984;Larkin et al, 1985], we find in the elderly both a general decline of anti-VZV antibody levels and a variable presence of different antibodies, and that antibodies to VZV gpll and the 155-kDa protein are con sistently present in the aged. In addition, sta tistical analysis indicated that the presence of anti-gpIV antibody detected in sera from patients with a past history of zoster was sig nificantly higher than in the sera from the elderly individuals without a history of zoster.…”

“…It has been shown that the major anti-VZV antibodies detected in sera from patients with varicella and zoster include antibodies to VZV glycoproteins (gpI-gpIV) and to three nonglycosylated pro teins of 155, 140 and 32 kDa [Weigle and Grose, 1984], In addition, the presence of antibodies to VZV proteins during the course of varicella and zoster has been ana lyzed by Weigle and Grose [1984] and Lar kin et al [1985], who showed that antibodies to VZV-specific proteins corresponding to these VZV proteins were present in human sera by approximately 5 weeks after the on set of rash. Furthermore, it has been shown that antibodies to gpll and the 155-kDa pro tein persists for years after acute varicella and zoster.…”

“…VZV contains four major glycoproteins capable of inducing neutralizing and CMI responses against VZV infection [Davison et al, 1986;Arvin etal., 1986], These glycopro teins are designated gpl through gpIV [Da vison et al, 1986], Antibodies to VZV glyco protein corresponding to gpll are detected by 2 weeks after clinical varicella followed by the detection of antibodies to other VZV gly coproteins and a 155-kilodalton (kDa) nonglycosylated protein by 5 weeks after the onset of rash [Weigle and Grose, 1984], In addition, antibodies to a 32-kDa protein are detected in sera from patients with recent zoster [Weigle and Grose, 1984], Except for antibodies to gpll and the 155-kDa protein, which persist for many years after primary infection and reactivation, antibodies to other VZV glycoproteins disappear shortly after varicella and zoster [Weigle and Grose, 1984;Larkin et al, 1985], This work is a retrospective analysis of humoral immunity in elderly individuals known to be at risk for zoster. In the present study, we analyzed sera from 40 individuals between 60 and 94 years of age for the pat tern of VZV-specific antibody expression.…”

Genome-Wide Analysis of T Cell Responses during Acute and Latent Simian Varicella Virus Infections in Rhesus Macaques

“…For instance, progressive varicella is most often reported in children with defects in cellular immunity or who are undergoing immunosuppressive treatment (7). In addition, children infected with HIV are at risk of prolonged viremia, continued formation of skin lesions, and dissemination of the virus to the lungs and other organs (7,8) and early production of VZV antibodies by HIVpositive (HIV ϩ ) children does not prevent progressive varicella (9). On the other hand, children with agammaglobulinemia have uncomplicated varicella episodes (10)(11).…”

Environmental chemical exposures and risk of herpes zoster.

“…It is also possible that many older retirees in Pinehurst have less contact with their extended families; therefore, they are less exposed to children with chickenpox than older persons in Aberdeen. Because contact with infectious carriers of the chickenpox virus boosts zoster-specific immunity among immunocompetent persons (28) Although the small sample size limited both the range of outcomes and the size of effects that could be studied, statistically significant associations between herpes zoster and age and steroid use provide some assurance that this study has the power to detect associations found in other studies. With 900 exposed and 742 unexposed participants and 4.5% of cases among the unexposed, the study had an 80% power to detect an overall RR of 1.8 (o = 0.05).…”