scholarly journals Human Papillomavirus type 16 L2 recruits both retromer and retriever complexes during retrograde trafficking of the viral genome to the cell nucleus.

2020 ◽  
Author(s):  
David Pim ◽  
Justyna Broniarczyk ◽  
Abida Siddiqa ◽  
Paola Massimi ◽  
Lawrence Banks
Keyword(s):  
Human Papillomavirus ◽  
Viral Genome ◽  
Direct Interaction ◽  
Hpv Infection ◽  
Infection Process ◽  
Sorting Nexins ◽  
Minor Capsid Protein ◽  
Human Papillomavirus Type 16 ◽  
Retromer Complex ◽  
Shed Light

Previous studies have identified an interaction between Human Papillomavirus L2 minor capsid protein and sorting nexins 17 and 27 (SNX17 and SNX27) during virus infection. Further studies show involvement of both retromer and retriever complexes in this process, since knockdown of proteins from either complex impairs infection. In this study, we show that HPV L2 and EdU-labelled pseudovirions colocalize with both retromer and retriever, with components of each complex being bound by L2 during infection. We also show that both sorting nexins may interact with either of the recycling complexes, but that the interaction between SNX17 and HPV16 L2 is not responsible for retriever recruitment during infection, instead being required for retromer recruitment. Further, we show that retriever recruitment most likely involves direct interaction between L2 and the C16orf62 subunit of retriever, in a similar manner to its interaction with the VPS35 subunit of retromer. IMPORTANCE Previous studies identified sorting nexins 17 and 27, as well as the retromer complex, as playing a role in HPV infection. This study shows that the newly-identified retriever complex also plays an important role and begins to shed light on how both sorting nexins contribute to retromer and retriever recruitment during the infection process.

scholarly journals Long-term Persistence of Oral Human Papillomavirus Type 16: The HPV Infection in Men (HIM) Study

2015 ◽  
Vol 8 (3) ◽  
pp. 190-196 ◽  
Author(s):  
Christine M. Pierce Campbell ◽  
Aimée R. Kreimer ◽  
Hui-Yi Lin ◽  
William Fulp ◽  
Michael T. O'Keefe ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Hpv Infection ◽  
Human Papillomavirus Type 16

scholarly journals Identification of a Dynein Interacting Domain in the Papillomavirus Minor Capsid Protein L2

2006 ◽  
Vol 80 (13) ◽  
pp. 6691-6696 ◽  
Author(s):  
Luise Florin ◽  
Katrin A. Becker ◽  
Carsten Lambert ◽  
Thorsten Nowak ◽  
Cornelia Sapp ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Papillomavirus ◽  
Capsid Protein ◽  
Viral Genome ◽  
Promyelocytic Leukemia ◽  
Protein Bodies ◽  
Viral Dna ◽  
Microtubule Network ◽  
Promyelocytic Leukemia Protein ◽  
Minor Capsid Protein

ABSTRACT Papillomaviruses enter cells via endocytosis (H. C. Selinka et al., Virology 299:279-287, 2002). After egress from endosomes, the minor capsid protein L2 accompanies the viral DNA to the nucleus and subsequently to the subnuclear promyelocytic leukemia protein bodies (P. M. Day et al., Proc. Natl. Acad. Sci. USA 101:14252-14257, 2004), suggesting that this protein may be involved in the intracytoplasmic transport of the viral genome. We now demonstrate that the L2 protein is able to interact with the microtubule network via the motor protein dynein. L2 protein was found attached to microtubules after uncoating of incoming human papillomavirus pseudovirions. Based on immunofluorescence and coimmunoprecipitation analyses, the L2 region interacting with dynein is mapped to the C-terminal 40 amino acids. Mutations within this region abrogating the L2/dynein interaction strongly reduce the infectivity of pseudoviruses, indicating that this interaction mediates the minus-end-directed transport of the viral genome along microtubules towards the nucleus.

scholarly journals Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus 16 cervical cancer isolates from China

2006 ◽  
Vol 87 (5) ◽  
pp. 1181-1188 ◽  
Author(s):  
Yuping Wu ◽  
Yulong Chen ◽  
Longyu Li ◽  
Guifang Yu ◽  
Ying He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Patients ◽  
Hpv Infection ◽  
Typing Method ◽  
Hpv16 E6 ◽  
Human Papillomavirus 16 ◽  
Human Papillomavirus Type 16 ◽  
New Variant

Human papillomavirus type 16 (HPV16) has a number of intratypic variants; each has a different geographical distribution and some are associated with enhanced oncogenic potential. Cervical samples were collected from 223 cervical cancer patients and from 196 age-matched control subjects in China. DNA samples were amplified by using primers specific for the E6, E7 and partial L1 regions. Products were sequenced and analysed. It was found by using a PCR–sequence-based typing method that HPV infection rates in China were 92·8 % in cervical cancer patients and 15·8 % in healthy controls. HPV16 was detected in 70·4 % of cervical cancer patients and in 6·1 % of controls. In HPV16-positive cervical cancers, 23·6 % belonged to the prototype, 65·5 % were of the Asian variant, 5·5 % were of African type 1 and 3·6 % were European variants, whilst only one was a new variant that differed from any variant published so far. Prevalences of HPV16 E6 D25E and E113D variants were 67·3 and 9 %, respectively. In addition to D25E and E113D, the following E6 variations were found in this study: R129K, E89Q, S138C, H78Y, L83V and F69L. The results also showed that the prevalences of three hot spots of E7 nucleotide variation, N29S, S63F and a silent variation, nt T846C, were 70·2 % (33/47), 51·1 % (24/47) and 61·7 % (29/47), respectively. The following L1 variations were found in this study: S377A, K387E, E378D, K382E and T379P. It was also found that the average age of Asian variant-positive cervical cancer patients (42·98±10·43 years) was 7·56 years lower than that of prototype-positive patients (50·54±10·91). It is suggested that the high frequency of HPV16 Asian variants might contribute to the high incidence of cervical cancer in China.

scholarly journals The E1 Protein of Human Papillomavirus Type 16 Is Dispensable for Maintenance Replication of the Viral Genome

2012 ◽  
Vol 86 (6) ◽  
pp. 3276-3283 ◽  
Author(s):  
N. Egawa ◽  
T. Nakahara ◽  
S.-i. Ohno ◽  
M. Narisawa-Saito ◽  
T. Yugawa ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Viral Genome ◽  
Human Papillomavirus Type 16 ◽  
E1 Protein

scholarly journals Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2

2017 ◽  
Author(s):  
Samuel K. Campos
Keyword(s):  
Human Papillomavirus ◽  
Paradigm Shift ◽  
Viral Genome ◽  
Retrograde Transport ◽  
Nuclear Accumulation ◽  
Subcellular Trafficking ◽  
Minor Capsid Protein ◽  
Initial Infection ◽  
Host Cell Proteins

Beginning in 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on a myriad of host cell proteins and processes. The major breakthrough finding from these recent endeavors was the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.

scholarly journals Cloning, Expression, and Purification of the rE2 Protein Human Papillomavirus type 16

2020 ◽  
pp. 1-5
Author(s):  
Saucedo Mendiola María Leticia ◽  
Keyword(s):  
Human Papillomavirus ◽  
Sexually Transmitted Disease ◽  
Reliable Method ◽  
Uterine Cancer ◽  
Transmitted Disease ◽  
Hpv Infection ◽  
Expression And Purification ◽  
Men And Women ◽  
Sexually Transmitted ◽  
Human Papillomavirus Type 16

Human papillomavirus (HPV) infection is the most common sexually transmitted disease, both in men and women, and the persistence of this infection is the main causative agent of cervical-uterine cancer. HPV 16 protein E2 is important in viral replication and transcription. For this reason, it is of utmost importance to have a reliable method of expression and purification of recombinant E2 (rE2) proteins to carry out experiments focused on the development of drugs against HPV.

scholarly journals Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns

2020 ◽  
Vol 10 ◽  
Author(s):  
Nikita Aggarwal ◽  
Joni Yadav ◽  
Kulbhushan Thakur ◽  
Rakhi Bibban ◽  
Arun Chhokar ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Human Papillomavirus ◽  
Head And Neck ◽  
Squamous Cell ◽  
Viral Genome ◽  
Surrogate Marker ◽  
Hpv Infection ◽  
Host Cells ◽  
Current Evidence ◽  
Cellular Environment

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers. Collectively, HNSCC ranks sixth in incidence rate worldwide. Apart from classical risk factors like tobacco and alcohol, infection of human papillomavirus (HPV) is emerging as a discrete risk factor for HNSCC. HPV-positive HNSCC represent a distinct group of diseases that differ in their clinical presentation. These lesions are well-differentiated, occur at an early age, and have better prognosis. Epidemiological studies have demonstrated a specific increase in the proportions of the HPV-positive HNSCC. HPV-positive and HPV-negative HNSCC lesions display different disease progression and clinical response. For tumorigenic-transformation, HPV essentially requires a permissive cellular environment and host cell factors for induction of viral transcription. As the spectrum of host factors is independent of HPV infection at the time of viral entry, presumably entry of HPV only selects host cells that are permissive to establishment of HPV infection. Growing evidence suggest that HPV plays a more active role in a subset of HNSCC, where they are transcriptionally-active. A variety of factors provide a favorable environment for HPV to become transcriptionally-active. The most notable are the set of transcription factors that have direct binding sites on the viral genome. As HPV does not have its own transcription machinery, it is fully dependent on host transcription factors to complete the life cycle. Here, we review and evaluate the current evidence on level of a subset of host transcription factors that influence viral genome, directly or indirectly, in HNSCC. Since many of these transcription factors can independently promote carcinogenesis, the composition of HPV permissive transcription factors in a tumor can serve as a surrogate marker of a separate molecularly-distinct class of HNSCC lesions including those cases, where HPV could not get a chance to infect but may manifest better prognosis.

scholarly journals TopBP1 Regulates Human Papillomavirus Type 16 E2 Interaction with Chromatin

2007 ◽  
Vol 81 (8) ◽  
pp. 4338-4342 ◽  
Author(s):  
Mary M. Donaldson ◽  
Winifred Boner ◽  
Iain M. Morgan
Keyword(s):  
Human Papillomavirus ◽  
Life Cycle ◽  
Viral Genome ◽  
Cellular Protein ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Human Papillomavirus Type 16 ◽  
Cellular Factors ◽  
Late Stages ◽  
Mitotic Chromatin

ABSTRACT Human papillomavirus type 16 (HPV16) E2 regulates transcription from and replication of the viral genome, in association with viral and cellular factors. HPV16 E2 interacts functionally with TopBP1, a cellular protein essential for the initiation of cellular, and potentially viral, DNA replication. This report demonstrates that the absence of TopBP1 results in the redistribution of HPV16 E2 into an alternative cellular protein complex, resulting in enhanced affinity for chromatin. This redistribution does not significantly alter the ability of HPV16 E2 to either activate or repress transcription. We also show colocalization of both proteins on chromatin at late stages of mitosis, suggesting that TopBP1 could be the mitotic chromatin receptor for HPV16 E2. The possible significance of the results for the regulation of the viral life cycle is discussed.

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