Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2

Hu, Yu-Wen; Rocheleau, Lynda; Larke, Bryce; Chui, Linda; Lee, Bonita; Ma, Mang; Liu, Song; Omlin, Teye; Pelchat, Martin; Brown, Earl G.

doi:10.1016/j.virol.2004.11.041

Cited by 34 publications

(23 citation statements)

References 44 publications

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“…Additionally, a continuous viral production leads to an increasing chance of detection by host immune system, and viral escape mechanisms are likely to be positively selected. In fact, Hepacivirus genus is known for its unique ability among Flaviviridae to modulate both innate and adaptive host immune system [80] as well as to mimic host proteins [81], [82] to avoid host immune system detection. For us it seems likely that the quasi-normal CpG and TpA frequencies in Hepacivirus genomic signature is a direct consequence of the viral escape mechanisms that were selected due to its persistence.…”

Section: Resultsmentioning

confidence: 99%

Virus-Host Coevolution: Common Patterns of Nucleotide Motif Usage in Flaviviridae and Their Hosts

et al. 2009

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Virus-host biological interaction is a continuous coevolutionary process involving both host immune system and viral escape mechanisms. Flaviviridae family is composed of fast evolving RNA viruses that infects vertebrate (mammals and birds) and/or invertebrate (ticks and mosquitoes) organisms. These host groups are very distinct life forms separated by a long evolutionary time, so lineage-specific anti-viral mechanisms are likely to have evolved. Flaviviridae viruses which infect a single host lineage would be subjected to specific host-induced pressures and, therefore, selected by them. In this work we compare the genomic evolutionary patterns of Flaviviridae viruses and their hosts in an attempt to uncover coevolutionary processes inducing common features in such disparate groups. Especially, we have analyzed dinucleotide and codon usage patterns in the coding regions of vertebrate and invertebrate organisms as well as in Flaviviridae viruses which specifically infect one or both host types. The two host groups possess very distinctive dinucleotide and codon usage patterns. A pronounced CpG under-representation was found in the vertebrate group, possibly induced by the methylation-deamination process, as well as a prominent TpA decrease. The invertebrate group displayed only a TpA frequency reduction bias. Flaviviridae viruses mimicked host nucleotide motif usage in a host-specific manner. Vertebrate-infecting viruses possessed under-representation of CpG and TpA, and insect-only viruses displayed only a TpA under-representation bias. Single-host Flaviviridae members which persistently infect mammals or insect hosts (Hepacivirus and insect-only Flavivirus, respectively) were found to posses a codon usage profile more similar to that of their hosts than to related Flaviviridae. We demonstrated that vertebrates and mosquitoes genomes are under very distinct lineage-specific constraints, and Flaviviridae viruses which specifically infect these lineages appear to be subject to the same evolutionary pressures that shaped their host coding regions, evidencing the lineage-specific coevolutionary processes between the viral and host groups.

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Section: Resultsmentioning

confidence: 99%

Virus-Host Coevolution: Common Patterns of Nucleotide Motif Usage in Flaviviridae and Their Hosts

et al. 2009

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“…Finally, the basis for the strong association between the immune response to HCV and the detection of an RF may lie in the structural and antigenic homologies between the N-terminal region of the HCV E2 envelope protein and the human immunoglobulin variable domains, and as such can be recognized by antihuman antibodies. 125,126 All the aforementioned microbial pathogens may also evade the immune system by antigenic variation, as has been documented in detail for H pylori, 57 B burgdorferi, 127 and HCV. 128 This process also contributes to chronic stimulation of the immune system by continuously modifying microbial antigenic determinants.…”

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confidence: 94%

Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation

Suarez

2006

Blood

398

296

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IntroductionThe geographic heterogeneity in the incidence of B-cell nonHodgkin lymphomas (NHLs) suggests that environmental factors such as infections might have a role in lymphomagenesis. 1,2 Because of the inherent genetic instability of lymphocytes, lymphoid proliferation increases the risk of transformation, and sustained activation of the lymphoid system, which can be observed during chronic infection, immunodeficiency, and autoimmunity, constitutes a risk factor for lymphomas. [3][4][5] Congenital and acquired immunodeficiencies associated with HIV infection and solid organ or hematopoietic transplantation increase the risk of developing B-cell NHLs. 6,7 Similarly, Sjögren syndrome and other autoimmune conditions are also associated with an increased risk of lymphomas. 8,9 Certain types of lymphomas are associated with specific microbial infections, and infection-associated lymphomas currently fall in diverse histopathologic categories (Table 1). 10 Infections may contribute to lymphomagenesis by promoting favorable conditions for lymphocyte transformation, such a increased proliferation or decreased apoptosis of lymphoid cells. 11 Direct lymphocyte transformation by a given microbial agent is the simplest scenario accounting for infection-associated lymphomas. Lymphotropic transforming viruses such as Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and human Tlymphotropic virus 1 (HTLV-1) directly infect a subset of lymphoid cells in which they express viral oncogenes. [12][13][14] An alternative scenario to direct transformation of lymphocytes has more recently emerged for microbial species associated with lymphomas but that do not directly infect or transform lymphoid cells. They have in common the ability to persist chronically in host tissues and trigger a sustained lymphoid proliferation, giving a selective advantage to lymphoid clones that still remain dependent upon antigen stimulation. 15,16 According to this model, the microbial pathogen is neither intrinsically transforming nor oncogenic, but can be viewed as a chronic source of antigens increasing the proliferative rate of lymphoid effectors, hence fueling the transformation process. This model has emerged with the description of several lymphomas developing in the context of chronic antigen-dependent immune stimulation, among which H pylori-associated gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the best characterized 15,17,18 (Figure 1). Precise elucidation of the mechanisms underlying this "indirect" lymphomagenesis as well as completion of the inventory of the microbial species driving these antigen-dependent lymphoproliferations may provide important clues for their early diagnosis and the rationalization of the therapeutic interventions for this subtype of lymphomas.This group of lymphomas often involves extranodal sitesnormally devoid of organized lymphoid tissue-and manifests initially as indolent low-grade proliferations, reminiscent of the normal lymphoid hyperplasia driven by a physiologic antigenic stimulation....

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“…The direct relationship between viral load, MCII, and tumor burden, as well as sequence analysis of the BCR from HCV-associated lymphomas [36], favors the hypothesis that cryoglobulins are produced by the tumor clone. The fact that there appears to be mimicry between the E2 protein and human immunoglobulin also supports this hypothesis [37], because antibodies against E2 probably crossreact with immunoglobulins and display RF activity. Thus, HCVassociated SLVL could represent a true model of antigen-driven lymphoma developing from a TI response.…”

mentioning

confidence: 65%