1.Mechanisms of herpes simplex virus latency and reactivation.
Boqiang SUN ; Qiongyan WANG ; Dongli PAN
Journal of Zhejiang University. Medical sciences 2019;48(1):89-101
Herpes simplex virus (HSV), including HSV-1 and HSV-2, is an important pathogen that can cause many diseases. Usually these diseases are recurrent and incurable. After lytic infection on the surface of peripheral mucosa, HSV can enter sensory neurons and establish latent infection during which viral replication ceases. Moreover, latent virus can re-enter the replication cycle by reactivation and return to peripheral tissues to start recurrent infection. This ability to escape host immune surveillance during latent infection and to spread during reactivation is a viral survival strategy and the fundamental reason why no drug can completely eradicate the virus at present. Although there are many studies on latency and reactivation of HSV, and much progress has been made, many specific mechanisms of the process remain obscure or even controversial due to the complexity of this process and the limitations of research models. This paper reviews the major results of research on HSV latency and reactivation, and discusses future research directions in this field.
Herpes Simplex
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virology
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Herpesvirus 1, Human
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physiology
;
Humans
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Virus Activation
;
physiology
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Virus Latency
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physiology
;
Virus Replication
2.Research Progress in Mechanisms Associated with Latent Infection in Humans by the Cytomegalovirus.
Huihui GAO ; Ran TAO ; Huimin YU ; Shiqiang SHANG
Chinese Journal of Virology 2016;32(1):82-87
The human cytomegalovirus (HCMV) is a widespread herpesvirus. Virus reactivation from latency can lead to stillbirth, miscarriage, fetal anomalies, and intrauterine growth retardation. During latent infection with the HCMV, the virus can be cleared by the immune response or apoptosis of host cells. However, the HCMV has developed several strategies to manipulate expression of its genes and the microenvironment of host cells. Recent studies have shown that latent infection with the HCMV is associated with viral: regulation of early expression of genes; evasion of cell death; evasion of the immune response; regulatin of non-coding RNAs. This review summarizes recent research progress on the mechanisms underpinning latent infection with the HCMV.
Animals
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Cytomegalovirus
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genetics
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physiology
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Cytomegalovirus Infections
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immunology
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virology
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Humans
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Viral Proteins
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genetics
;
metabolism
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Virus Latency
3.Latent infection of human herpes virus in hematopoietic system.
Ke-Fu WU ; Xiao-Tong MA ; Guo-Guang ZHENG ; Yu-Hua SONG
Journal of Experimental Hematology 2008;16(6):1251-1256
Up to date, eight types of human herpes viruses have been identified, all of which are ubiquitous, and usually establish latent infection in the host after primary infection. Since most of the herpes viruses are maintained in an asymptomatic form, they are often neglected. However, under some circumstances, these herpes viruses can cause fatal or severe diseases. Furthermore, the association of herpes viruses with hematopoietic malignancies is attracting researchers' attention. With the extensive development of hematopoietic stem cell and organ transplantation, reports regarding transplantation failure and complication caused by infection of human herpes virus has been increasing. Cytokine storm was firstly suggested as the mechanism of graft-versus-host diseases. In recent years, which has also been applied in the pathogenesis research of inflammation, and is supposed to play an important role in severe virus infection. In this paper, through discussing the possible role of latent infection of human herpes virus in the failure or complication of bone marrow or hematopoietic stem cell transplantation, and in refractory leukemia, the function and significance of latent infection of human herpes virus and the cytokine storm it caused were investigated.
Cytokines
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immunology
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Hematopoietic System
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immunology
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virology
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Herpesviridae Infections
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Humans
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Virus Latency
4.Research advances on anti-apoptosis effect of herpes simplex virus latency-associated transcripts.
Hui-Lan YANG ; Li-Li BAI ; Jian-Yong FAN
Chinese Journal of Virology 2010;26(1):76-79
Animals
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Apoptosis
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Herpes Simplex
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physiopathology
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virology
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Humans
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MicroRNAs
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genetics
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metabolism
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Simplexvirus
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genetics
;
physiology
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Virus Latency
5.Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure.
Silvere D ZAONGO ; Yue WANG ; Ping MA ; Fang-Zhou SONG ; Yao-Kai CHEN
Chinese Medical Journal 2021;134(23):2776-2787
Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as "selective elimination of host cells capable of producing HIV" (SECH). Similar to the "shock and kill strategy," the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.
CD4-Positive T-Lymphocytes
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HIV Infections/drug therapy*
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HIV-1
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Humans
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Virus Latency
6.Heterogeneity of HIV-1 latent reservoirs.
Chinese Medical Journal 2020;133(23):2867-2873
Antiretroviral therapy (ART) can effectively inhibit human immunodeficiency virus-1 (HIV-1) replication, but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruses. In order to reduce or eliminate the HIV-1 latent reservoir, characteristics of the latently infected cells need to be intensively studied, and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic strategies. Here, we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs, and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome (AIDS).
CD4-Positive T-Lymphocytes
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HIV Infections/drug therapy*
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HIV-1
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Humans
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Viral Load
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Virus Latency
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Virus Replication
7.Efficacy of Acyclovir on Replication in Infected Tissues and Virus Reactivation from Explanted Tissues in Mouse Encephalitis Model of Herpes Simplex Virus Type 1.
Chong Kyo LEE ; Jee Hyun KIM ; Pan Kee BAE ; Mi Kyung PI ; Hae Soo KIM
Journal of the Korean Society of Virology 1999;29(3):165-174
To investigate viral pathogenesis and in vivo efficacy of acyclovir (ACV) in mouse HSV-1 encephalitis models, female BALB/c mice aged 5 weeks were inoculated with strain F either intranasally (IN) or intracerebrally (IC). ACV-treatment by intraperitorneal injection with 0, 5, 10 and 25 mg/kg b.i.d. for 6days was commenced 1 h after infection. Body weight and signs of clinical disease were noted daily up to 2 weeks. ED50 of ACV in IN infection was 5mg/kg and 14.1 mg/kg in IC infection. Tissues of cental nervous system were collected from 2 mice per group everyday up to 5 days p.i. and the virus titers were measured. In IN infection model, high titers in eyes and trigeminal nerves were observed. ACV-treatment showed significant reduction of the titers in all the isolated. In IC infection model, cerebrum, cerebellum and brain stem showed high virus titers. ACV-treatment showed less significant reduction of virus titers than that in IN infection model. Reactivation of explanted trigeminal nerves from mice 30 day p.i. was monitored. In all of ACV treated mice reactivation was observed, i.e. even the highest dose of ACV did not inhibit the establishment of viral latency.
Acyclovir*
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Animals
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Body Weight
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Brain Stem
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Cerebellum
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Cerebrum
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Encephalitis*
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Female
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Herpes Simplex*
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Herpesvirus 1, Human*
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Humans
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Mice*
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Nervous System
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Simplexvirus*
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Trigeminal Nerve
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Virus Latency
8.Retrospective cohort study on period of incubation and survival among former commercial plasma donors infected with HIV in Hebei province.
Su-liang CHEN ; Guang-yi BAI ; Qiao-min LI ; Bao-jun LI ; Yan-liang HUI ; Liang LIANG ; Wei WANG ; Zhi-qiang CHEN ; Xin-li LU ; Xiao-feng WANG ; Yu-qi ZHANG ; Hong-ru ZHAO
Chinese Journal of Preventive Medicine 2012;46(4):316-319
OBJECTIVETo examine the state of incubation period and survival time of former commercial plasma donors (FCPDs) infected with HIV.
METHODSAll objects infected with HIV were from Hebei province and found from general investigation for FCPDs in 1995. The infector cohort by 142 cases was used to estimate incubation period. In the infector cohort, the time which infectors entered the cohort was their infection time, which was the middle value of the origin date, which was January 1, 1995. The onset of AIDS was defined as an outcome event. End point of observation was Dec 31, 2010. There were 192 months in all from beginning to end. The AIDS cohort by 57 cases was used to estimate the survival of the patients. In the patient cohort, the time of AIDS onset was defined as the time entering the cohort, and death of AIDS was defined as an outcome event. The cumulative incidence ratio, cumulative mortality, illness intensity and mortality intensity were analyzed through Kaplan-Meier.
RESULTSDuring the observation period, 123 cases of 142 infectors developed into AIDS, the cumulative incidence was 86.42% (123/142) and the intensity was 8.53/100 person-years and the median time of incubation period was 112.0 months (95%CI: 108.8 - 115.2). The death dates of 57 patients were from 1 to 24 months after onset. The cumulative mortality was 100%, and the intensity was 250.66/100 person-years and the median survival time was 3.0 months (95%CI: 1.8 - 4.2). It was estimated that the median time was 115.0 months (9.6 years) from infection to death.
CONCLUSIONThe median times of incubation and median survival time were 112.0 and 3.0 months, respectively.
Adult ; Blood Donors ; Cohort Studies ; Female ; HIV ; physiology ; HIV Infections ; epidemiology ; mortality ; virology ; Humans ; Incidence ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Virus Latency ; Young Adult
9.Epstein-Barr virus latent genes.
Myung Soo KANG ; Elliott KIEFF
Experimental & Molecular Medicine 2015;47(1):e131-
Latent Epstein-Barr virus (EBV) infection has a substantial role in causing many human disorders. The persistence of these viral genomes in all malignant cells, yet with the expression of limited latent genes, is consistent with the notion that EBV latent genes are important for malignant cell growth. While the EBV-encoded nuclear antigen-1 (EBNA-1) and latent membrane protein-2A (LMP-2A) are critical, the EBNA-leader proteins, EBNA-2, EBNA-3A, EBNA-3C and LMP-1, are individually essential for in vitro transformation of primary B cells to lymphoblastoid cell lines. EBV-encoded RNAs and EBNA-3Bs are dispensable. In this review, the roles of EBV latent genes are summarized.
Epstein-Barr Virus Infections/complications/virology
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Epstein-Barr Virus Nuclear Antigens/genetics/metabolism
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*Genes, Viral
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Herpesvirus 4, Human/*physiology
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Humans
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MicroRNAs/genetics
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Neoplasms/etiology
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Protein Binding
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RNA, Viral/genetics
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Viral Matrix Proteins/genetics/metabolism
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*Virus Latency
10.Expression of herpes simplex virus type 2 latency associated transcript ORF1 and its anti-apoptotic function.
Fangbiao LV ; Huilan YANG ; Feifei ZHONG ; Jianyong FAN ; Yanhua LIU ; Ruidi GAO
Chinese Journal of Biotechnology 2013;29(12):1776-1785
To study the expression of herpes simplex virus type 2 latency-associated transcript (LAT) open reading frame 1 (ORF1) and its anti-apoptosis function induced by actinomycin D in Vero cells. The recombinant plasmid pEGFP-ORF1 was constructed and transfected into Vero cells, and the expression of ORF1 was identified by RT-PCR. The changes of Vero cells morphology induced by actinomycin D were observed by fluorescence microscopy, Hochest33258 fluorescence staining. Cells viability was evaluated by MTT assay and cells apoptosis rate was detected by flow cytometry. Double digestion and sequencing confirmed the pEGFP-ORF1 was constructed successfully, RT-PCR showed that the target gene was highly expressed in Vero cells. Hochest33258 staining reaveals that Vero cells transfected with pEGFP-ORF1 and induced apoptosis by actinomycin D had no changes in morphology. MTT assay showed that the viabilities of Vero cells transfected with recombinant plasmid pEGFP-ORF1 and induced apoptosis by actinomycin D has no statistically significant difference compared with the untreated normal control group (P > 0.05), but remarkable higher than Vero cells transfected with empty plasmid pEGFP-C2 and induced apoptosis by actinomycin D, the difference was statistically significant (P < 0.05). Flow cytometry assay shows that the cells apoptosis rate had no significant difference between pEGFP-ORF1 group and the normal group, but the cells apoptosis rate ofpEGFP-ORF1 was lower than the pEGFP-C2 group. HSV-2 LAT ORF1 gene can be expressed in Vero cells and can protect Vero cells from apoptosis induced by actinomycin D.
Animals
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Apoptosis
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physiology
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Cercopithecus aethiops
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Dactinomycin
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Herpes Simplex Virus Protein Vmw65
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genetics
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Herpesvirus 2, Human
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genetics
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Open Reading Frames
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genetics
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Promoter Regions, Genetic
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Transcription, Genetic
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Vero Cells
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Viral Proteins
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genetics
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Virus Activation
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Virus Latency
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genetics
;
physiology