Abstract:
:It is well established that chronic viral infections can cause immune suppression, resulting in increased susceptibility to other infectious diseases. However, the effects of chronic viral infection on T-cell responses and vaccination against highly pathogenic viruses are not well understood. We have recently shown that C57BL/6 (B6) mice lose their natural resistance to wild-type (WT) ectromelia virus (ECTV) when chronically infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13). Here we compared the T-cell response to ECTV in previously immunologically naive mice that were chronically infected with CL13 or that were convalescent from acute infection with the Armstrong (Arm) strain of LCMV. Our results show that mice that were chronically infected with CL13 but not those that had recovered from Arm infection have highly defective ECTV-specific CD8+ and CD4+ T-cell responses to WT ECTV. These defects are at least partly due to the chronic infection environment. In contrast to mice infected with WT ECTV, mice chronically infected with CL13 survived without signs of disease when infected with ECTV-Δ036, a mutant ECTV strain that is highly attenuated. Strikingly, mice chronically infected with CL13 mounted a strong CD8+ T-cell response to ECTV-Δ036 and survived without signs of disease after a subsequent challenge with WT ECTV. Our work suggests that enhanced susceptibility to acute viral infections in chronically infected individuals can be partly due to poor T-cell responses but that sufficient T-cell function can be recovered and resistance to acute infection can be restored by immunization with highly attenuated vaccines.IMPORTANCE Chronic viral infections may result in immunosuppression and enhanced susceptibility to infections with other pathogens. For example, we have recently shown that mice chronically infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) are highly susceptible to mousepox, a disease that is caused by ectromelia virus and that is the mouse homolog of human smallpox. Here we show chronic CL13 infection severely disrupts the expansion, proliferation, activation, and cytotoxicity of T cells in response due at least in part to the suppressive effects of the chronic infection milieu. Notably, despite this profound immunodeficiency, mice chronically infected with CL13 could be protected by vaccination with a highly attenuated variant of ECTV. These results demonstrate that protective vaccination of immunosuppressed individuals is possible, provided that proper immunization tools are used.
journal_name
J Viroljournal_title
Journal of virologyauthors
Alves-Peixoto P,Férez M,Knudson CJ,Melo-Silva CR,Stotesbury C,Wong EB,Correia-Neves M,Sigal LJdoi
10.1128/JVI.01832-19subject
Has Abstractpub_date
2020-02-14 00:00:00issue
5eissn
0022-538Xissn
1098-5514pii
JVI.01832-19journal_volume
94pub_type
杂志文章abstract::Previous work on the strict late (gamma) UL38 promoter of herpes simplex virus type 1 identified three cis-acting elements required for wild-type levels of transcription: a TATA box at -31, a consensus mammalian initiator element at the transcription start site, and a downstream activation sequence (DAS) at +20 to +33...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.8181-8190.1998
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abstract::A consensus binding site for the human papillomavirus (HPV) E2 protein was determined from an unbiased set of degenerate oligonucleotides using cyclic amplification and selection of targets (CASTing). Detectable DNA-protein complexes were formed after six to nine cycles of CASTing. A population of selected binding sit...
journal_title:Journal of virology
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doi:10.1128/JVI.75.4.1722-1735.2001
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journal_title:Journal of virology
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doi:10.1128/JVI.00040-09
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02639-07
更新日期:2008-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1800-1802.1989
更新日期:1989-04-01 00:00:00
abstract::The nucleoprotein of the WSN strain of influenza was found to be phosphorylated in vitro. The phosphate-protein bond was stable to hot trichloroacetic acid, RNase, DNase, succinic acid, and succinic acid-hydroxylamine, but sensitive to hydrolysis by bacterial alkaline phosphatase. This suggested that the nucleoprotein...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.24.1.401-405.1977
更新日期:1977-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.19.2.374-381.1976
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00789-09
更新日期:2009-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00858-11
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.27.1.164-171.1978
更新日期:1978-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02540-10
更新日期:2011-05-01 00:00:00
abstract::The Kaposi's sarcoma-associated herpesvirus nuclear egress complex is composed of two proteins, ORF67 and ORF69. In this study, we have recapitulated the KSHV complex by coexpression of these two proteins in insect cells using expression from recombinant baculoviruses. The proteins form a complex at the nuclear membra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05988-11
更新日期:2012-01-01 00:00:00
abstract::The genome of infectious hematopoietic necrosis virus (IHNV), a salmonid novirhabdovirus, has been engineered to modify the gene order and to evaluate the impact on a possible attenuation of the virus in vitro and in vivo By reverse genetics, eight recombinant IHNVs (rIHNVs), termed NxGy according to the respective po...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01024-16
更新日期:2016-11-14 00:00:00
abstract::Therapeutic strategies for the treatment of acute retroviral infections have relied mainly on antiviral drugs. In this study we used the Friend virus model system to demonstrate that enhancement of the immune system can also have dramatic therapeutic effects. Since resistance to Friend virus-induced leukemia in mice i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.22.11397-11404.2002
更新日期:2002-11-01 00:00:00
abstract::H9N2 avian influenza virus (AIV) has an extended host range, but the molecular basis underlying H9N2 AIV transmission to mammals remains unclear. We isolated more than 900 H9N2 AIVs in our 3-year surveillance in live bird markets in China from 2009 to 2012. Thirty-seven representative isolates were selected for furthe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01141-16
更新日期:2016-10-14 00:00:00
abstract::Murine gammaherpesvirus 68 (gammaHV68; also known as MHV-68) can establish a latent infection in both inbred and outbred strains of mice and, as such, provides a tractable small-animal model to address mechanisms and cell types involved in the establishment and maintenance of chronic gammaherpesvirus infection. Latenc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.15.8310-8321.2003
更新日期:2003-08-01 00:00:00
abstract::An E1-E3-deleted recombinant adenovirus vector expressing the hybrid protein TetR-KRAB has been produced. In this virus, AdTG9562, the E2 transcription is regulated by TetR-KRAB and tetO sequences inserted in cis. In the absence of tetracycline, a strong reduction in E2A gene expression, viral DNA replication, and lat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.4.3307-3311.1997
更新日期:1997-04-01 00:00:00
abstract::Monomers of the genomic strand of hepatitis delta virus RNA were transcribed in vitro and then delivered to NIH 3T3 fibroblasts by using a liposome fusion technique. After 7 days, genome replication was detected, but only in fibroblasts that stably expressed the delta antigen. Sequence analysis of the replicated produ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.6.3104-3107.1990
更新日期:1990-06-01 00:00:00
abstract::The TAATGARAT motif in the herpes simplex virus (HSV) immediate-early (IE) gene promoters plays a key role in their activation by the Oct-1-Vmw65 complex, but its role in mediating inhibitory effects of cellular octamer-binding proteins is less clear. We have used indicator viruses containing reporter constructs with ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.4.3495-3500.1998
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abstract::The major capsid protein of polyomavirus, VP1, was separated into at least four subspecies by isoelectric focusing. One of these subspecies was selectively extracted from purified virions by mild treatment with sodium dodecyl sulfate, leaving a 140S particle enriched in the other three forms. The two most acidic subsp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.2.311-316.1985
更新日期:1985-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.15.10003-10012.2005
更新日期:2005-08-01 00:00:00
abstract::Multispecific CD8(+) T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.20.12979-12988.2005
更新日期:2005-10-01 00:00:00
abstract::The mammalian APOBEC3 proteins are an important component of the cellular innate immune response to retroviral infection. APOBEC3G can extinguish HIV-1 infectivity by its incorporation into virus particles and subsequent cytosine deaminase activity that attacks the nascent viral cDNA during reverse transcription, caus...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00056-10
更新日期:2010-07-01 00:00:00
abstract::Four genetic loci were tested for linkage with loci that control genetic resistance to lethal ectromelia virus infection in mice. Three of the loci were selected because of concordance with genotypes assigned to recombinant inbred (RI) strains of mice derived from resistant C57BL/6 and susceptible DBA/2 (BXD) mice on ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.4.1946-1951.1991
更新日期:1991-04-01 00:00:00
abstract::Resistance or susceptibility of various mouse strains to central nervous system disease caused by different strains of coronavirus is well known. Data from the present study draw attention to an additional, genetically determined mechanism controlling CV infections. The resistance to A59 and JHM virus (JHMV) associate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3371-3377.1988
更新日期:1988-09-01 00:00:00
abstract::Purified Friend viruses obtained from chronically infected tissue cultures were studied under the electron microscope in an effort to correlate the fine structure of the particles to their leukemogenic activity under varied experimental conditions, i.e., temperature treatments and exposure to Tween 80, amyl acetate, o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.4.365-375.1968
更新日期:1968-04-01 00:00:00
abstract::Mutants of bacteriophage T4D that are defective in genes 42 (dCMP hydroxymethylase), 46 (DNA exonuclease), and 56 (dCTPase) produce limited amounts of phage DNA in Escherichia coli B. In this DNA, glucoylated 5-hydroxymethylcytosine is completely replaced by cytosine. We found that this DNA rapidly becomes fragmented ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.48.1.18-30.1983
更新日期:1983-10-01 00:00:00
abstract::The largest tegument protein of herpes simplex virus 1 (HSV-1), UL36, contains a novel deubiquitinating activity embedded in it. All members of the Herpesviridae contain a homologue of HSV-1 UL36, the N-terminal segments of which show perfect conservation of those residues implicated in catalysis. For murine cytomegal...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.24.15582-15585.2005
更新日期:2005-12-01 00:00:00
abstract::Recently, significant numbers of individuals with primary human immunodeficiency virus (HIV) infection have been found to harbor viral strains with reduced susceptibility to antiretroviral drugs. In one study, HIV from 16% of such antiretroviral-naive individuals was shown to have a susceptibility to nonnucleoside rev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.22.10269-10273.2000
更新日期:2000-11-01 00:00:00
abstract::A number of full-length cDNA clones of Kunjin virus (KUN) were previously prepared; it was shown that two of them, pAKUN and FLSDX, differed in specific infectivities of corresponding in vitro transcribed RNAs by approximately 100,000-fold (A. A. Khromykh et al., J. Virol. 72:7270-7279, 1998). In this study, we analyz...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.14.7804-7813.2003
更新日期:2003-07-01 00:00:00