The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

Castro-Muñoz, Leonardo Josué; Manzo-Merino, Joaquín; Muñoz-Bello, J. Omar; Olmedo-Nieva, Leslie; Cedro‐Tanda, Alberto; Alfaro-Ruiz, Luis; Hidalgo-Miranda, Alfredo; Madrid‐Marina, Vicente; Lizano, Marcela

doi:10.1038/s41598-019-49886-4

Cited by 37 publications

(22 citation statements)

References 59 publications

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“…The manipulation of IFN signaling by HPVs subsequently leads to the suppression of ISG expression. Analysis of patient biopsies and cell lines has identified Mx1, IFI56, OAS, ISG15, IFIT1, IFITM, RIG-I and MDA5 as prominent ISGs whose expression is suppressed by HPV proteins [ 82 , 86 , 109 , 125 , 127 , 128 ]. Most of the studies on IFNs and ISGs have been performed on cells with established HPV infections, and the events that occur during viral entry are not yet fully understood.…”

Section: Hpvs Alter Innate Immune Pathwaysmentioning

confidence: 99%

Human Papillomaviruses Target the DNA Damage Repair and Innate Immune Response Pathways to Allow for Persistent Infection

Gusho

Laimins

2021

Viruses

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Persistent infection with high-risk human papillomaviruses (HPVs) is the major risk factor associated with development of anogenital and oropharyngeal cancers. Initial infection by HPVs occurs into basal epithelial cells where viral genomes are established as nuclear episomes and persist until cleared by the immune response. Productive replication or amplification occurs upon differentiation and is dependent upon activation of the ataxia-telangiectasia mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) DNA damage repair (DDR) pathways. In addition to activating DDR pathways, HPVs must escape innate immune surveillance mechanisms by antagonizing sensors, adaptors, interferons and antiviral gene expression. Both DDR and innate immune pathways are key host mechanisms that crosstalk with each other to maintain homeostasis of cells persistently infected with HPVs. Interestingly, it is still not fully understood why some HPV infections get cleared while others do not. Targeting of these two processes with antiviral therapies may provide opportunities for treatment of cancers caused by high-risk HPVs.

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Section: Hpvs Alter Innate Immune Pathwaysmentioning

confidence: 99%

Human Papillomaviruses Target the DNA Damage Repair and Innate Immune Response Pathways to Allow for Persistent Infection

Gusho

Laimins

2021

Viruses

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“…Given the anti-viral nature of ISGs, HPV have multiple mechanisms for blocking the JAK-STAT pathway to prevent their activation of ISGs. Four viral proteins, when overexpressed, can repress ISG expression: E6, E7, E1 and E2 [ 20 , 47 , 74 , 75 ].…”

Section: Hpv and Repression Of The Innate Immune Response (Iir)mentioning

confidence: 99%

Activating the DNA Damage Response and Suppressing Innate Immunity: Human Papillomaviruses Walk the Line

et al. 2020

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Activation of the DNA damage response (DDR) by external agents can result in DNA fragments entering the cytoplasm and activating innate immune signaling pathways, including the stimulator of interferon genes (STING) pathway. The consequences of this activation can result in alterations in the cell cycle including the induction of cellular senescence, as well as boost the adaptive immune response following interferon production. Human papillomaviruses (HPV) are the causative agents in a host of human cancers including cervical and oropharyngeal; HPV are responsible for around 5% of all cancers. During infection, HPV replication activates the DDR in order to promote the viral life cycle. A striking feature of HPV-infected cells is their ability to continue to proliferate in the presence of an active DDR. Simultaneously, HPV suppress the innate immune response using a number of different mechanisms. The activation of the DDR and suppression of the innate immune response are essential for the progression of the viral life cycle. Here, we describe the mechanisms HPV use to turn on the DDR, while simultaneously suppressing the innate immune response. Pushing HPV from this fine line and tipping the balance towards activation of the innate immune response would be therapeutically beneficial.

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“…Early region includes E1, E2, E4, E5, E6, and E7 protein coding part which are regularly in function and plays important role in HPV oncogenicity. E1 participates in HPV DNA replication process (Castro-Muñoz et al 2019 ), along with E2; E2 also works as transcription activator and regulator (Oliveira et al 2006 ), E4 (Yajid et al 2017 ); (Doorbar 2013 ) and E5 modulates the productive phase of HPV life cycle (Müller et al 2015 ). E5, E6 and E7 are considered as the major hallmarks of HPV infection, these three are also essential for the development of HPV positive carcinoma (Estêvão et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive in Silico Analysis for Identification of Immunotherapeutic Epitopes of HPV-18

Gupta

Kumar²,

Sridevi

2021

Int J Pept Res Ther

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Human papillomavirus (HPV) remains the major cause of cervical cancer, globally. High risk HPV (Hr-HPV) 16 and 18 together account for more than 70% of cervical cancer cases, whereas the hr-HPV-18 is the second most prevalent hr-HPV type, causing about 5.2% of all cancers worldwide. Considering the high prevalence and mortality rate, cervical cancer remains a noteworthy health problem among women. As of now, no registered immunotherapies are available after the HPV infection. Thus, developing an immunotherapeutic candidate against hr-HPV would be of major clinical benefit. Nowadays, the T-and B-cell peptide based targeted vaccines have been considered as the best candidate for vaccine development against viral infections. In this study, both prophylactic and therapeutic vaccine candidates against hr-HPV-18 were predicted. To achieve this, the prediction of T-and B-cell epitopes of major histocompatibility complex (MHC) were accomplished, that can be used for HPV immunotherapy. For MHC-I, a maximum number (20) of potent peptides were found, against HLA-B*51:01 (L1 = 9, L2 = 6, E2 = 4, and E4 = 1) having percentile value < 1 and, immunogenicity scores higher than 0.5, followed by HLA-A*11:01 (L1 = 8, E2 = 7 L2 = 2, and E6 = 1, E7 = 1); 19 epitopes. For MHC-II, the highest number of peptides found, against the HLA-DRB1*04:01 (L2 = 10, E5 = 7, and E4 = 4), HLA-DRB1*04:05 (E5 = 7, E2 = 5, E4 = 5, and L1 = 4) HLA-DPA1*01:03/DPB1*04:01 (E7 = 7, E6 = 5, L2 = 5, and E2 = 2), HLA-DRB5*01:01(E6 = 6, L1 = 6, and L2 = 6); peptides 21, 21, 19 and 18 respectively. For B-cell, total 94, 16 amino acid long B-cell epitopes were predicted. In conclusion, these predicted epitopes can be valuable candidates for in vitro or in vivo therapeutic vaccine studies against hr-HPV-18 associated cancer.

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The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

Cited by 37 publications

References 59 publications

Human Papillomaviruses Target the DNA Damage Repair and Innate Immune Response Pathways to Allow for Persistent Infection

Human Papillomaviruses Target the DNA Damage Repair and Innate Immune Response Pathways to Allow for Persistent Infection

Activating the DNA Damage Response and Suppressing Innate Immunity: Human Papillomaviruses Walk the Line

A Comprehensive in Silico Analysis for Identification of Immunotherapeutic Epitopes of HPV-18

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