scholarly journals APOBECs and Herpesviruses

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Adam Z. Cheng ◽  
Sofia N. Moraes ◽  
Nadine M. Shaban ◽  
Elisa Fanunza ◽  
Craig J. Bierle ◽  
...  
Keyword(s):  
Dna Replication ◽  
Viral Infections ◽  
Degradation Mechanism ◽  
Herpes Simplex Virus 1 ◽  
New Host ◽  
Viral Pathogens ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Replication Intermediates

The APOBEC family of DNA cytosine deaminases provides a broad and overlapping defense against viral infections. Successful viral pathogens, by definition, have evolved strategies to escape restriction by the APOBEC enzymes of their hosts. HIV-1 and related retroviruses are thought to be the predominant natural substrates of APOBEC enzymes due to obligate single-stranded DNA replication intermediates, abundant evidence for cDNA strand C-to-U editing (genomic strand G-to-A hypermutation), and a potent APOBEC degradation mechanism. In contrast, much lower mutation rates are observed in double-stranded DNA herpesviruses and the evidence for APOBEC mutation has been less compelling. However, recent work has revealed that Epstein-Barr virus (EBV), Kaposi’s sarcoma herpesvirus (KSHV), and herpes simplex virus-1 (HSV-1) are potential substrates for cellular APOBEC enzymes. To prevent APOBEC-mediated restriction these viruses have repurposed their ribonucleotide reductase (RNR) large subunits to directly bind, inhibit, and relocalize at least two distinct APOBEC enzymes – APOBEC3B and APOBEC3A. The importance of this interaction is evidenced by genetic inactivation of the EBV RNR (BORF2), which results in lower viral infectivity and higher levels of C/G-to-T/A hypermutation. This RNR-mediated mechanism therefore likely functions to protect lytic phase viral DNA replication intermediates from APOBEC-catalyzed DNA C-to-U deamination. The RNR-APOBEC interaction defines a new host-pathogen conflict that the virus must win in real-time for transmission and pathogenesis. However, partial losses over evolutionary time may also benefit the virus by providing mutational fuel for adaptation.

Select Viruses in Adults

2012 ◽  
pp. 61-79
Author(s):  
Randall C. Walker
Keyword(s):  
Viral Infections ◽  
Parvovirus B19 ◽  
Systemic Disease ◽  
Diagnostic Tools ◽  
Varicella Zoster ◽  
Epidemiologic Factors ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

The following types of viral infections are discussed in this chapter: viral infections that have the capacity for multiorgan or systemic disease; infections that affect adults who may be otherwise healthy or at least not in special populations such as herpes simplex virus (HSV) type 1, varicella-zoster virus (VZV), Epstein-Barr virus, adenovirus, mumps virus, human parvovirus B19, and coxsackievirus. Reviews of these viruses focus on differentiating clinical features, diagnostic tools and treatment, and salient microbiologic and epidemiologic factors.

scholarly journals An overview of viral infections of the nervous system in the immunosuppressed

2020 ◽  
Author(s):  
Peter G. E. Kennedy
Keyword(s):  
Nervous System ◽  
Measles Virus ◽  
Viral Infections ◽  
Jc Virus ◽  
Virus Infections ◽  
Inborn Errors ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

Abstract Several viruses have the capacity to cause serious infections of the nervous system in patients who are immunosuppressed. Individuals may be immunosuppressed because of primary inherited immunodeficiency, secondary immunodeficiency due to particular diseases such as malignancy, administration of immunosuppressant drugs or organ or bone marrow transplantation. The viruses capable of such opportunistic infection of the nervous system include herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein –Barr virus (EBV), Human Herpes virus type 6 (HHV-6), JC virus (JCV), enterovirus, measles virus and Covid-19. In most cases it seems likely that immunological defence mechanisms in the immunosuppressed are deficient which creates a suitable environment for certain viruses to become opportunistic in the nervous and other systems. Further research is required both to understand these opportunistic mechanisms in more detail and also to determine how many virus infections are modified by specific inborn errors of immunological responses.

A Survey of Serum Antibodies to Eight Common Viruses in Psychiatric Patients

1985 ◽  
Vol 147 (2) ◽  
pp. 137-144 ◽  
Author(s):  
D. J. King ◽  
S. J. Cooper ◽  
J. A. P. Earle ◽  
S. J. Martin ◽  
N. V. McFerran ◽  
...  
Keyword(s):  
Viral Infections ◽  
Psychiatric Patients ◽  
Serum Antibody ◽  
Later Life ◽  
Barr Virus ◽  
Neurotropic Viruses ◽  
Antibody Titres ◽  
The Central Nervous System ◽  
Epstein Barr ◽  
Simplex Virus

SummarySerum antibody titres to eight neurotropic viruses were measured by enzyme immunoassay in 450 psychiatric in-patients and 143 controls. A seasonal variation in schizophrenic births was observed, with a peak incidence between March and April. Both herpes simplex virus and cytomegalovirus antibody titres correlated with age and, when this was controlled for, no significant differences emerged between any patient group and the controls. Mumps antibody titres were significantly lower in patients with mental subnormal and neurosis or personality disorder; measles and rubella antibody titres were lower in male but not female mentally handicapped patients; males had lower antibody titres to mumps, cytomegalovirus and Epstein-Barr virus than females in all groups. A decrease in mumps antibody titres was also found in schizophrenics if the medication factor was excluded. These low antibody titres may indicate an impaired immune response. Thus perinatal or childhood subclinical viral infections of the central nervous system, particularly of mumps, might lead to a range of possible psychiatric outcomes in later life.

scholarly journals Epstein-Barr Virus mRNA Export Factor EB2 Is Essential for Production of Infectious Virus

2002 ◽  
Vol 76 (19) ◽  
pp. 9635-9644 ◽  
Author(s):  
Henri Gruffat ◽  
Julien Batisse ◽  
Dagmar Pich ◽  
Bernhard Neuhierl ◽  
Evelyne Manet ◽  
...  
Keyword(s):  
Dna Replication ◽  
Nuclear Export ◽  
Epstein Barr Virus ◽  
Alternative Pathway ◽  
Virus Production ◽  
Gene Encoding ◽  
Barr Virus ◽  
Cytoplasmic Accumulation ◽  
Epstein Barr ◽  
Simplex Virus

ABSTRACT The splicing machinery which positions a protein export complex near the exon-exon junction mediates nuclear export of mRNAs generated from intron-containing genes. Many Epstein-Barr virus (EBV) early and late genes are intronless, and an alternative pathway, independent of splicing, must export the corresponding mRNAs. Since the EBV EB2 protein induces the cytoplasmic accumulation of intronless mRNA, it is tempting to speculate that EB2 is a viral adapter involved in the export of intronless viral mRNA. If this is true, then the EB2 protein is essential for the production of EBV infectious virions. To test this hypothesis, we generated an EBV mutant in which the BMLF1 gene, encoding the EB2 protein, has been deleted (EBVBMLF1-KO). Our studies show that EB2 is necessary for the production of infectious EBV and that its function cannot be transcomplemented by a cellular factor. In the EBVBMLF1-KO 293 cells, oriLyt-dependent DNA replication was greatly enhanced by EB2. Accordingly, EB2 induced the cytoplasmic accumulation of a subset of EBV early mRNAs coding for essential proteins implicated in EBV DNA replication during the productive cycle. Two herpesvirus homologs of the EB2 protein, the herpes simplex virus type 1 protein ICP27 and, the human cytomegalovirus protein UL69, only partly rescued the phenotype of the EBVBMLF1-KO mutant, indicating that some EB2 functions in virus production cannot be transcomplemented by ICP27 and UL69.

scholarly journals Characterization and Intracellular Trafficking of Epstein-Barr Virus BBLF1, a Protein Involved in Virion Maturation

2012 ◽  
Vol 86 (18) ◽  
pp. 9647-9655 ◽  
Author(s):  
Ya-Fang Chiu ◽  
Bill Sugden ◽  
Pey-Jium Chang ◽  
Lee-Wen Chen ◽  
Ying-Ju Lin ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Retrograde Transport ◽  
Lytic Replication ◽  
Herpes Simplex Virus 1 ◽  
Virus Particles ◽  
Tegument Proteins ◽  
Barr Virus ◽  
Viral Maturation ◽  
Epstein Barr ◽  
Simplex Virus

Epstein-Barr virus (EBV) BBLF1 shares 13 to 15% amino acid sequence identities with the herpes simplex virus 1 UL11 and cytomegalovirus UL99 tegument proteins, which are involved in the final envelopment during viral maturation. This study demonstrates that BBLF1 is a myristoylated and palmitoylated protein, as are UL11 and UL99. Myristoylation of BBLF1 both facilitates its membrane anchoring and stabilizes it. BBLF1 is shown to localize to thetrans-Golgi network (TGN) along with gp350/220, a site where final envelopment of EBV particles takes place. The localization of BBLF1 at the TGN requires myristoylation and two acidic clusters, which interact with PACS-1, a cytosolic protein, to mediate retrograde transport from the endosomes to the TGN. Knockdown of the expression of BBLF1 during EBV lytic replication reduces the production of virus particles, demonstrating the requirement of BBLF1 to achieve optimal production of virus particles. BBLF1 is hypothesized to facilitate the budding of tegumented capsid into glycoprotein-embedded membrane during viral maturation.

scholarly journals Stimulation of the Replication of ICP0-Null Mutant Herpes Simplex Virus 1 and pp71-Deficient Human Cytomegalovirus by Epstein-Barr Virus Tegument Protein BNRF1

2016 ◽  
Vol 90 (21) ◽  
pp. 9664-9673 ◽  
Author(s):  
Yongxu Lu ◽  
Anne Orr ◽  
Roger D. Everett
Keyword(s):  
Epstein Barr Virus ◽  
Nuclear Bodies ◽  
Regulatory Proteins ◽  
Tegument Protein ◽  
Null Mutant ◽  
Herpes Simplex Virus 1 ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT It is now well established that several cellular proteins that are components of promyelocytic leukemia nuclear bodies (PML NBs, also known as ND10) have restrictive effects on herpesvirus infections that are countered by viral proteins that are either present in the virion particle or are expressed during the earliest stages of infection. For example, herpes simplex virus 1 (HSV-1) immediate early (IE) protein ICP0 overcomes the restrictive effects of PML-NB components PML, Sp100, hDaxx, and ATRX while human cytomegalovirus (HCMV) IE protein IE1 targets PML and Sp100, and its tegument protein pp71 targets hDaxx and ATRX. The functions of these viral regulatory proteins are in part interchangeable; thus, both IE1 and pp71 stimulate the replication of ICP0-null mutant HSV-1, while ICP0 increases plaque formation by pp71-deficient HCMV. Here, we extend these studies by examining proteins that are expressed by Epstein-Barr virus (EBV). We report that EBV tegument protein BNRF1, discovered by other investigators to target the hDaxx/ATRX complex, increases the replication of both ICP0-null mutant HSV-1 and pp71-deficient HCMV. In addition, EBV protein EBNA-LP, which targets Sp100, also augments ICP0-null mutant HSV-1 replication. The combination of these two EBV regulatory proteins had a greater effect than each one individually. These findings reinforce the concept that disruption of the functions of PML-NB proteins is important for efficient herpesvirus infections. IMPORTANCE Whether a herpesvirus initiates a lytic infection in a host cell or establishes quiescence or latency is influenced by events that occur soon after the viral genome has entered the host cell nucleus. Certain cellular proteins respond in a restrictive manner to the invading pathogen's DNA, while viral functions are expressed that counteract the cell-mediated repression. One aspect of cellular restriction of herpesvirus infections is mediated by components of nuclear structures known as PML nuclear bodies (PML NBs), or ND10. Members of the alpha-, beta-, and gammaherpesvirus families all express proteins that interact with, degrade, or otherwise counteract the inhibitory effects of various PML NB components. Previous work has shown that there is the potential for a functional interchange between the viral proteins expressed by alpha- and betaherpesviruses, despite a lack of obvious sequence similarity. Here, this concept is extended to include a member of the gammaherpesviruses.

scholarly journals Enterovirus and herpesviridae family as etiologic agents of lymphomonocytary meningitis, Southern Brazil

2011 ◽  
Vol 69 (3) ◽  
pp. 475-481 ◽  
Author(s):  
Luine Rosele Renaud Vidal ◽  
Sérgio Monteiro de Almeida ◽  
Iara José de Messias-Reason ◽  
Meri Bordignon Nogueira ◽  
Maria do Carmo Debur ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Herpes Virus ◽  
Viral Meningitis ◽  
Etiologic Agent ◽  
Herpes Simplex Virus 1 ◽  
Virus Family ◽  
Barr Virus ◽  
Epstein Barr ◽  
Herpès Virus ◽  
Simplex Virus

Viral meningitis is a common infectious disease of the central nervous system (CNS) that occurs worldwide. The aim of this study was to identify the etiologic agent of lymphomonocytary meningitis in Curitiba, PR, Brazil. During the period of July 2005 to December 2006, 460 cerebrospinal fluid (CSF) samples with lymphomonocytary meningitis were analyzed by PCR methodologies. Fifty nine (12.8%) samples were positive. Enteroviruses was present in 49 (83%) samples and herpes virus family in 10 (17%), of these 6 (10%) herpes simplex virus, 1 (2%) Epstein Barr virus, 2 (3%) human herpes virus type 6 and 1 (2%) mixed infection of enterovirus and Epstein Barr virus. As conclusion enterovirus was the most frequent virus, with circulation during summer and was observed with higher frequency between 4 to 17 years of age. PCR methodology is an important method for rapid detection of RNA enterovirus and DNA herpesvirus in CSF.

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