Pathogens

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Open AccessReview

Epstein-Barr Virus Sequence Variation—Biology and Disease

by Stelios Tzellos and Paul J. Farrell

Pathogens 2012, 1(2), 156-174; https://doi.org/10.3390/pathogens1020156 - 08 Nov 2012

Cited by 109 | Viewed by 10345

Some key questions in Epstein-Barr virus (EBV) biology center on whether naturally occurring sequence differences in the virus affect infection or EBV associated diseases. Understanding the pattern of EBV sequence variation is also important for possible development of EBV vaccines. At present EBV [...] Read more.

Some key questions in Epstein-Barr virus (EBV) biology center on whether naturally occurring sequence differences in the virus affect infection or EBV associated diseases. Understanding the pattern of EBV sequence variation is also important for possible development of EBV vaccines. At present EBV isolates worldwide can be grouped into Type 1 and Type 2, a classification based on the EBNA2 gene sequence. Type 1 EBV is the most prevalent worldwide but Type 2 is common in parts of Africa. Type 1 transforms human B cells into lymphoblastoid cell lines much more efficiently than Type 2 EBV. Molecular mechanisms that may account for this difference in cell transformation are now becoming clearer. Advances in sequencing technology will greatly increase the amount of whole EBV genome data for EBV isolated from different parts of the world. Study of regional variation of EBV strains independent of the Type 1/Type 2 classification and systematic investigation of the relationship between viral strains, infection and disease will become possible. The recent discovery that specific mutation of the EBV EBNA3B gene may be linked to development of diffuse large B cell lymphoma illustrates the importance that mutations in the virus genome may have in infection and human disease. Full article

(This article belongs to the Special Issue Infection and Cancer)

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Open AccessReview

From Exit to Entry: Long-term Survival and Transmission of Salmonella

by Landon L. Waldner, Keith D. MacKenzie, Wolfgang Köster and Aaron P. White

Pathogens 2012, 1(2), 128-155; https://doi.org/10.3390/pathogens1020128 - 24 Oct 2012

Cited by 35 | Viewed by 9495

Abstract

Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella [...] Read more.

Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella outside their hosts. This review focuses on three areas: (1) in vitro evidence that Salmonella spp. can survive for long periods of time under harsh conditions; (2) observations and conclusions about Salmonella persistence obtained from human outbreaks; and (3) new information revealed by genomic- and population-based studies of Salmonella and related enteric pathogens. We highlight the mechanisms of Salmonella persistence and transmission as an essential part of their lifecycle and a prerequisite for their evolutionary success as human pathogens. Full article

(This article belongs to the Special Issue Feature Papers)

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Open AccessReview

Exploitation of Cellular Cytoskeletons and Signaling Pathways for Cell Entry by Kaposi’s Sarcoma-Associated Herpesvirus and the Closely Related Rhesus Rhadinovirus

by Wei Zhang and Shou-Jiang Gao

Pathogens 2012, 1(2), 102-127; https://doi.org/10.3390/pathogens1020102 - 22 Oct 2012

Cited by 7 | Viewed by 6867

Abstract

As obligate intracellular pathogens, viruses depend on the host cell machinery to complete their life cycle. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenicvirus causally linked to the development of Kaposi’s sarcoma and several other lymphoproliferative malignancies. KSHV entry into cells is tightly [...] Read more.

As obligate intracellular pathogens, viruses depend on the host cell machinery to complete their life cycle. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenicvirus causally linked to the development of Kaposi’s sarcoma and several other lymphoproliferative malignancies. KSHV entry into cells is tightly regulated by diverse viral and cellular factors. In particular, KSHV actively engages cellular integrins and ubiquitination pathways for successful infection. Emerging evidence suggests that KSHV hijacks both actin and microtubule cytoskeletons at different phases during entry into cells. Here, we review recent findings on the early events during primary infection of KSHV and its closely related primate homolog rhesus rhadinovirus with highlights on the regulation of cellular cytoskeletons and signaling pathways that are important for this phase of virus life cycle. Full article

(This article belongs to the Special Issue Infection and Cancer)

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Open AccessArticle

Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas

by Katerina Vrzalikova, Sarah Leonard, Yichao Fan, Andrew Bell, Martina Vockerodt, Patrik Flodr, Kenneth L. Wright, Martin Rowe, Qian Tao and Paul G. Murray

Pathogens 2012, 1(2), 83-101; https://doi.org/10.3390/pathogens1020083 - 08 Oct 2012

Cited by 10 | Viewed by 7535

Abstract

B-lymphocyte-induced maturation protein 1 (BLIMP1) exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC) B cell differentiation. In contrast, [...] Read more.

B-lymphocyte-induced maturation protein 1 (BLIMP1) exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC) B cell differentiation. In contrast, the shorter β isoform is functionallyimpaired and over-expressed in several haematological malignancies, including diffuse large B cell lymphomas (DLBCL). We have studied the influence on BLIMP1β expression of the Epstein-Barr virus (EBV), a human herpesvirus that is implicated in the pathogenesis of several GC-derived lymphomas, including a subset of DLBCL and Hodgkin’s lymphoma (HL). We show that BLIMP1β expression is increased following the EBV infection of normal human tonsillar GC B cells. We also show that this change in expression is accompanied by hypomethylation of the BLIMP1β-specific promoter. Furthermore, we confirmed previous reports that the BLIMP1β promoter is hypomethylated in DLBCL cell lines and show for the first time that BLIMP1β is hypomethylated in the Hodgkin/Reed-Sternberg (HRS) cells of HL. Our results provide evidence in support of a role for BLIMP1β in the pathogenesis of EBV-associated B cell lymphomas. Full article

(This article belongs to the Special Issue Infection and Cancer)

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990 KiB

Open AccessArticle

Chemoresistance to Valproate Treatment of Bovine Leukemia Virus-Infected Sheep; Identification of Improved HDAC Inhibitors

by Nicolas Gillet, Fabian Vandermeers, Alix De Brogniez, Arnaud Florins, Annamaria Nigro, Carole François, Amel-Baya Bouzar, Olivier Verlaeten, Eric Stern, Didier M. Lambert, Johan Wouters and Luc Willems

Pathogens 2012, 1(2), 65-82; https://doi.org/10.3390/pathogens1020065 - 08 Oct 2012

Cited by 8 | Viewed by 7157

Abstract

We previously proved that a histone deacetylase inhibitor (valproate, VPA) decreases the number of leukemic cells in bovine leukemia virus (BLV)-infected sheep. Here, we characterize the mechanisms initiated upon interruption of treatment. We observed that VPA treatment is followed by a decrease of [...] Read more.

We previously proved that a histone deacetylase inhibitor (valproate, VPA) decreases the number of leukemic cells in bovine leukemia virus (BLV)-infected sheep. Here, we characterize the mechanisms initiated upon interruption of treatment. We observed that VPA treatment is followed by a decrease of the B cell counts and proviral loads (copies per blood volume). However, all sheep eventually relapsed after different periods of time and became refractory to further VPA treatment. Sheep remained persistently infected with BLV. B lymphocytes isolated throughout treatment and relapse were responsive to VPA-induced apoptosis in cell culture. B cell proliferation is only marginally affected by VPA ex vivo. Interestingly, in four out of five sheep, ex vivo viral expression was nearly undetectable at the time of relapse. In two sheep, a new tumoral clone arose, most likely revealing a selection process exerted by VPA in vivo. We conclude that the interruption of VPA treatment leads to the resurgence of the leukemia in BLV-infected sheep and hypothesize that resistance to further treatment might be due to the failure of viral expression induction. The development of more potent HDAC inhibitors and/or the combination with other compounds can overcome chemoresistance. These observations in the BLV model may be important for therapies against the related Human T-lymphotropic virus type 1. Full article

(This article belongs to the Special Issue Infection and Cancer)

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Pathogens, Volume 1, Issue 2 (December 2012) – 5 articles , Pages 65-174

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