Viral persistence: mechanisms and consequences

Oldstone, Michael B. A.

doi:10.1016/s1369-5274(98)80062-3

Cited by 35 publications

(19 citation statements)

References 57 publications

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“…Many infectious agents, ranging from viruses to parasites, have evolved to develop several mechanisms to subvert immune surveillance and to establish themselves chronically in the host [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

et al. 2005

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The ability of a microorganism to elicit or evade B cell responses represents a determinant factor for the final outcome of an infection. Although pathogens may subvert humoral responses at different stages of B cell development, most studies addressing the impact of an infection on the B cell compartment have focused on mature B cells within peripheral lymphoid organs. Herein, we report that a protozoan infection, i.e. a Trypanosoma cruzi infection, induces a marked loss of immature B cells in the BM, which also compromises recently emigrated B cells in the periphery. The depletion of BM immature B cells is associated with an increased rate of apoptosis mediated by a parasite-indirect mechanism in a Fas/FasL-independent fashion. Finally, we demonstrated that myeloid cells play an important role in B cell depletion, since CD11b + BM cells from infected mice secrete a product of the cyclooxygenase pathway that eliminates immature B cells. These results highlight a previously unrecognized maneuver used by a protozoan parasite to disable B cell generation, limiting host defense and favoring its chronic establishment.

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Section: Introductionmentioning

confidence: 99%

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

et al. 2005

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“…In addition, LCMV provides one of the most widely used model systems to study viral persistence and pathogenesis (7,10,37,38,39,40,45).…”

mentioning

confidence: 99%

RING Finger Z Protein of Lymphocytic Choriomeningitis Virus (LCMV) Inhibits Transcription and RNA Replication of an LCMV S-Segment Minigenome

Cornu

Torre

2001

J Virol

134

120

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Arenaviruses have a bisegmented negative-strand RNA genome whose proteomic capability is limited to only four polypeptides, namely, nucleoprotein (NP), surface glycoprotein (GP) that is proteolytically processed into GP1؉GP2, polymerase (L), and a small (11-kDa) RING finger protein (Z). The role of Z during the Lymphocytic choriomeningitis virus (LCMV) life cycle is poorly understood. We investigated the function of Z in virus transcription and replication by using a reverse genetic system for the prototypic arenavirus LCMV. This system involves an LCMV minigenome and the minimal viral trans-acting factors (NP and L), expressed from separated cotransfected plasmids. Cotransfection of the Z cDNA strongly inhibited LCMV minigenome expression. The effect required synthesis of Z protein; its magnitude was dose dependent and occurred with levels of Z protein substantially lower than those observed in LCMV-infected cells. Coexpression of Z did not prevent the encapsidation of plasmid supplied minigenome, but it affected both transcription and RNA replication similarly. Mutations in Z that unfolded its RING finger domain eliminated its inhibitory activity, but RING proteins not related to Z did not affect LCMV minigenome expression. Consistent with the minigenome results, cells transiently expressing Z exhibited decreased susceptibility to infection with LCMV. Lymphocytic choriomeningitis virus (LCMV)is the prototypic member of the family Arenaviridae, which includes important human pathogens such as Lassa fever and Junin viruses (11,41,43,53,55). In addition, LCMV provides one of the most widely used model systems to study viral persistence and pathogenesis (7,10,37,38,39,40,45).The LCMV genome consists of two negative-sense singlestranded RNA segments, L and S, with approximate sizes of 7.2 and 3.4 kb, respectively (44,48,52,53). Each RNA segment has an ambisense coding strategy, encoding two proteins in opposite orientations, separated by an intergenic region (IGR) (48, 53). The S RNA directs synthesis of the three major structural proteins: the nucleoprotein, NP (ca. 63 kDa) (44,48,53), and the two virion glycoproteins, GP-1 (40 to 46 kDa) and GP-2 (35 kDa), which are derived by posttranslational cleavage of a precursor polypeptide, GP-C (75 kDa) (48,53,54,60). Tetramers of GP-1 and GP-2 make up the spikes on the virion envelope and mediate virus interaction with host cell surface receptor (6, 13). The L RNA segment encodes a high-molecular-mass protein (L, ca. 200 kDa) (52), which has the characteristic motifs conserved in all of the viral RNA-dependent RNA polymerases (46), and a small (11-kDa) RING finger protein (Z) (50). The NP, the most abundant viral protein in virus-infected cells, is associated with the viral RNA to form the nucleocapsid (NC), which is the template for the viral RNA polymerase (23,24). The L protein is thought to be the main viral component of the arenavirus polymerase (23,48,53). The NC associated with the viral polymerase constitutes the viral ribonucleoprotein (RNP), which is active in ...

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“…Viruses may mediate protection through secretion of immunoregulatory cytokines such as IL-10 or TGFβ to hamper the host's immune system, which results in decreased inflammation and increased activity of regulatory cell subsets, thereby inducing a certain degree of tolerance towards itself but also reducing immunopathology and presumably the risk of developing autoimmune disease in the host. 44,45 Parasites have been suggested to mediate protection through induction of iNKT cells as well as skewing the CD4 T cell responses from cytotoxic Th1 responses towards Th2 responses. [46][47][48] Thus, protective exposure to microbial agents or other environmental factors may reinforce the immune system's delicate balance between effector and regulatory functions and thereby educate the immune system to better deal with potential disease triggering influences (Fig.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%