Race between Retroviral Spread and CD4<sup>+</sup>T-Cell Response Determines the Outcome of Acute Friend Virus Infection

Pike, Rebecca; Filby, Andrew; Ploquin, Mickaël J.-Y.; Eksmond, Urszula; Marques, Rute; Antunes, Inês; Hasenkrug, Kim J.; Kassiotis, George

doi:10.1128/jvi.01225-09

Cited by 32 publications

(50 citation statements)

References 62 publications

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“…Endocytosis-competent Tetherin did not influence T cell responses in the B 1 cohort, possibly because 7 dpi may be too early to detect potent T cell responses (42, 43). Since LDV-free FV can significantly induce Tetherin expression, B6 WT (n=16) and B6 Tetherin KO (n=15) mice were infected with 10 4 SFFU of LDV-free FV, and samples were harvested at 14 dpi.…”

Section: Resultsmentioning

confidence: 93%

“…CD8+ and CD4+ T cell responses are critical for recovery from FV infection (33, 42, 43, 54, 55) and these T cell responses peak shortly after 7 dpi (56, 57). Thus, the relatively weak association between Tetherin and T cell responses in the B 1 experiments led us to perform a second set of studies, this time with B6 WT and B6 Tetherin KO mice at 14 dpi.…”

Section: Discussionmentioning

confidence: 99%

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Tetherin Promotes the Innate and Adaptive Cell–Mediated Immune Response against Retrovirus Infection In Vivo

Barrett

Heilman

et al. 2014

The Journal of Immunology

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Tetherin/BST-2 is a host restriction factor that could directly inhibit retroviral particle release by tethering nascent virions to the plasma membrane. However, the immunological impact of Tetherin during retrovirus infection remains unknown. We now show that Tetherin influences antiretroviral cell-mediated immune responses. In contrast to the direct antiviral effects of Tetherin, which are dependent on cell surface expression, the immunomodulatory effects are linked to the endocytosis of the molecule. Mice encoding endocytosis-competent C57BL/6 Tetherin exhibited lower viremia and pathology at 7 days post-infection with Friend retrovirus (FV) compared to mice encoding endocytosis-defective NZW/LacJ Tetherin. Notably, antiretroviral protection correlated with stronger NK cell responses. In addition, FV infection levels were significantly lower in wild-type C57BL/6 mice than in Tetherin knock-out mice at 2 weeks post-infection, and antiretroviral protection correlated with stronger NK cell and virus-specific CD8+ T cell responses. The results demonstrate that Tetherin acts as a modulator of the cell-mediated immune response against retrovirus infection in vivo.

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Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Tetherin Promotes the Innate and Adaptive Cell–Mediated Immune Response against Retrovirus Infection In Vivo

Barrett

Heilman

et al. 2014

The Journal of Immunology

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“…First, and probably foremost, the primary effector in vaccinated hosts are antibodies, 17 whereas the primary effector in our 12-d infections are T cells. 37,38 Plasmodium escape from the initial humoral response could cause subsequent infections in both vaccinated and unvaccinated mice to be more virulent because critical B-cell epitopes have been eliminated. Second, all of these malaria studies operate on a very different experimental paradigm than our study.…”

Section: Discussionmentioning

confidence: 99%

Host resistance influences patterns of experimental viral adaptation and virulence evolution

Kubinak¹,

Potts²

2013

Virulence

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“…Depending on genotypes at several host loci, some strains of mice can eliminate virus-producing cells and recover from splenomegaly, while others progress rapidly to fatal pathology (1,3,5). Results from several research groups largely agree on the role of virus-neutralizing antibodies and CD4 ϩ T cells in immune control of FV infection (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Natural killer cells also contribute to FV elimination and are essential for vaccine-induced protection of highly susceptible mice (8,16).…”

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Elimination of Friend Retrovirus in the Absence of CD8⁺T Cells

Tsuji-Kawahara

Miyazawa

2014

J Virol

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Friend retrovirus complex (FV) induces acute erythroid cell hyperplasia and massive splenomegaly followed by the emergence of fatal erythroleukemia upon inoculation into adult mice of susceptible strains (1-3). Because the disease can progress in the presence of host immune responses, FV has served as a useful model to study how retroviruses evade immune control (1,3,4). Depending on genotypes at several host loci, some strains of mice can eliminate virus-producing cells and recover from splenomegaly, while others progress rapidly to fatal pathology (1,3,5). Results from several research groups largely agree on the role of virus-neutralizing antibodies and CD4 ϩ T cells in immune control of FV infection (6-15). Natural killer cells also contribute to FV elimination and are essential for vaccine-induced protection of highly susceptible mice (8, 16). However, there are conflicting views on the role of CD8 ϩ T cells in FV control. Earlier studies associated major histocompatibility complex class I (MHC-I) alleles with spontaneous recovery from FVinduced splenomegaly, and FV-specific, CD8ϩ cytotoxic T cells were detected (1, 5). Further, the recovery in H2 b mice was abrogated when CD8 ϩ T cells were depleted (6). On the other hand, by using FV-encoded epitopes recognized by CD4 ϩ T cells as peptide vaccines, we have shown that highly susceptible (BALB/c ϫ C57BL/6)F 1 mice can still be protected from FV challenge and eliminate virus-producing cells in the absence of CD8 ϩ T cells (9). Interestingly, MHC-I genotypes influenced cytokine production from CD4 ϩ T cells upon FV infection (17, 18), indicating the possible indirect role of CD8 ϩ T cells. C57BL/6 (B6) mice lack the expression of a short form of hematopoietic cell-specific receptor tyrosine kinase, Stk, and do not develop FV-induced erythroid cell proliferation (19). Some reports have indicated that CD8 ϩ T cells are essential in controlling FV infection in B6 mice, as infectious centers at an early time point after FV infection increased upon depletion of CD8 ϩ T cells (20)(21)(22). However, infectious centers were detected in the above-described reports with monoclonal antibody 720 (23) that reacts only with the helper component of FV, Friend murine leukemia virus (F-MuLV), but not with the pathogenic component, the spleen focus-forming virus (SFFV). In our recent work (24), SFFV was eliminated from B6 mice by 2 weeks after infection, and CD8 ϩ T cell-deficient B6 mice remained resistant to FV-induced disease development. Thus, the increase of F-MuLV infectious centers after CD8 ϩ T cell depletion, albeit statistically significant, may not reflect pathologically significant changes in SFFV load.Here, we examined changes in SFFV copy numbers in CD8 ϩ T cell-deficient B6 mice after FV infection. CD8 ϩ T cell-deficient B6 mice nevertheless eliminated both F-MuLV and SFFV proviruses, though more slowly than the wild-type B6 mice did, as shown in Fig. 1. Thus, while CD8 ϩ T cells do contribute to control FV infection, they are not essential for the elimination o...

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Race between Retroviral Spread and CD4⁺T-Cell Response Determines the Outcome of Acute Friend Virus Infection

Cited by 32 publications

References 62 publications

Tetherin Promotes the Innate and Adaptive Cell–Mediated Immune Response against Retrovirus Infection In Vivo

Tetherin Promotes the Innate and Adaptive Cell–Mediated Immune Response against Retrovirus Infection In Vivo

Host resistance influences patterns of experimental viral adaptation and virulence evolution

Elimination of Friend Retrovirus in the Absence of CD8⁺T Cells

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Race between Retroviral Spread and CD4+T-Cell Response Determines the Outcome of Acute Friend Virus Infection

Cited by 32 publications

References 62 publications

Tetherin Promotes the Innate and Adaptive Cell–Mediated Immune Response against Retrovirus Infection In Vivo

Tetherin Promotes the Innate and Adaptive Cell–Mediated Immune Response against Retrovirus Infection In Vivo

Host resistance influences patterns of experimental viral adaptation and virulence evolution

Elimination of Friend Retrovirus in the Absence of CD8+T Cells

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Product

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Race between Retroviral Spread and CD4⁺T-Cell Response Determines the Outcome of Acute Friend Virus Infection

Elimination of Friend Retrovirus in the Absence of CD8⁺T Cells