Cytotoxic T cell recognition of tegument and regulatory proteins encoded by open reading frames (ORFs) 4, 10, 29, and 62 of varicella-zoster virus (VZV) was evaluated using limiting dilution conditions to estimate the precursor frequencies of memory T cells specific for these proteins in immune subjects. Responder cell frequencies for ORFs 4, 10, and 62 gene products, which are virion tegument components and function as immediate early viral transactivating proteins, were equivalent. CTLp recognition of VZV proteins made in latently infected cells, which include ORF4 and ORF62 proteins, was not maintained preferentially when compared to ORF10 protein, which has not been shown to be expressed during latency. T cell recognition of ORF29 protein, the major DNA binding protein, which is expressed during replication but not incorporated into the virion tegument, was less common than responses to ORFs 4, 10, and 62 gene products. Older individuals had diminished numbers of memory CTLp that lysed autologous targets expressing IE62 protein; these responses were increased after immunization with live attenuated varicella vaccine to the range observed in younger adults. Adaptive immunity to VZV is characterized by a broad repertoire of memory CTL responses to proteins that comprise the virion tegument and regulate viral gene expression in infected cells.

Download full-text PDF

Source
http://dx.doi.org/10.1089/088282402760312377DOI Listing

Publication Analysis

Top Keywords

virion tegument
12
cytotoxic cell
8
tegument regulatory
8
regulatory proteins
8
proteins encoded
8
encoded open
8
open reading
8
reading frames
8
varicella-zoster virus
8
cell recognition
8

Similar Publications

Mapping the Protein Phosphatase 1 Interactome in Human Cytomegalovirus Infection.

Viruses

December 2024

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria.

Protein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterization of the PP1 interactome during HCMV infection and its alterations.

View Article and Find Full Text PDF

Unlabelled: Herpesviruses carry an assortment of proteins in the interstitial space between the capsid and membrane envelope, collectively referred to as the tegument. Upon virion fusion with a cell, envelope integrity is disrupted, and many tegument constituents disperse into the cytosol to carry out individual effector functions, while others direct transport of the capsid to the nucleus. To gain insight into the tegument dynamics that occur with disruption of envelope integrity, we used a combination of single-particle fluorescence and biochemical approaches that leveraged the previously established use of n-ethylmaleimide to inhibit virion dynamics.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers successfully created an infectious clone of HSV-1 by assembling its genome from 11 cloned fragments in yeast using a method called transformation associated recombination.* -
  • They engineered mutations in five specific genes, which are important for the virus's structure and functionality, and discovered that certain combinations of these mutations led to "synthetic lethality," preventing the virus from replicating in specific cell lines.* -
  • The study focused on the mutations of the UL16 and UL21 genes, revealing that viruses lacking both proteins showed immature capsid structures unable to mature into infectious particles, highlighting their potential roles in virus assembly.*
View Article and Find Full Text PDF

Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins.

Nat Metab

December 2024

Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

As obligate intracellular pathogens, viruses activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of salvage nicotinamide adenine dinucleotide (NAD) synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses through unknown mechanisms. Here, we show that NAMPT restricts herpes simplex virus type 1 (HSV-1) replication by impeding the virion incorporation of viral proteins owing to its phosphoribosyl-hydrolase (phosphoribosylase) activity, which is independent of the role of NAMPT in NAD synthesis.

View Article and Find Full Text PDF
Article Synopsis
  • The study focuses on the structural characterization of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), two members of the gammaherpesvirus subfamily known for their tumorigenicity, using advanced techniques like deep learning-enhanced cryogenic electron tomography (cryoET).
  • It reveals unique features of the viruses, such as their pleomorphic characteristics, the positioning of their nucleocapsids, and the composition of their envelopes, which differ significantly from alpha- and betaherpesviruses.
  • This research provides insights into the architecture of these viruses, which may influence their infection processes and cell tropism, enhancing our understanding of human herpesviruses and their roles in cancer.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!