Major histocompatibility complex class I-restricted cytotoxic T lymphocyte responses during primary simian immunodeficiency virus infection in Burmese rhesus macaques

Nakamura, Midori; Takahara, Yusuke; Ishii, Hiroshi; Sakawaki, Hiromi; Horiike, Mariko; Miura, Tomoyuki; Igarashi, Tatsuhiko; Naruse, Taeko K.; Kimura, Akinori; Matano, Tetsuro; Matsuoka, Satomi

doi:10.1111/j.1348-0421.2011.00384.x

Cited by 4 publications

(6 citation statements)

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“…3). All of these E ϩ unvaccinated macaques elicited immunodominant Nef-specific CD8 ϩ T-cell responses, consistent with our previous study analyzing other E ϩ macaques (50). Gag-specific and Vif-specific CD8 ϩ T-cell responses were detected but were not immunodominant in these animals.…”

Section: Plasma Viral Loads After Sivmac239 Challengesupporting

confidence: 91%

“…The Nef [45][46][47][48][49][50][51][52][53] region is a candidate for a CD8 ϩ T-cell target associated with MHC-I haplotype E, and the NefL53P mutation resulting in escape from Nef 45-53 -specific CD8 ϩ T-cell recognition was often selected in E ϩ animals. These results imply suppressive pressure on SIV replication by Nef-specific CD8 ϩ T-cell responses in macaques sharing this MHC-I haplotype.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in the Nef 45-53 -coding region were selected after 1 year in five of seven unvaccinated E ϩ animals. Rapid selection of mutations at this Nef [45][46][47][48][49][50][51][52][53] -coding region in a month after SIV challenge was observed in both Gag-vaccinated noncontrollers and all three Vif/Nef-vaccinated noncontrollers (Fig. 5C).…”

Section: Plasma Viral Loads After Sivmac239 Challengementioning

confidence: 92%

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Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 ⁺ T Cells

Iwamoto

Takahashi

Seki

et al. 2014

J Virol

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dFor development of an effective T cell-based AIDS vaccine, it is critical to define the antigens that elicit the most potent responses. Recent studies have suggested that Gag-specific and possibly Vif/Nef-specific CD8 ؉ T cells can be important in control of the AIDS virus. Here, we tested whether induction of these CD8 ؉ T cells by prophylactic vaccination can result in control of simian immunodeficiency virus (SIV) replication in Burmese rhesus macaques sharing the major histocompatibility complex class I (MHC-I) haplotype 90-010-Ie associated with dominant Nef-specific CD8 ؉ T-cell responses. In the first group vaccinated with Gag-expressing vectors (n ‫؍‬ 5 animals), three animals that showed efficient Gag-specific CD8؉ T-cell responses in the acute phase postchallenge controlled SIV replication. In the second group vaccinated with Vif-and Nef-expressing vectors (n ‫؍‬ 6 animals), three animals that elicited Vif-specific CD8 ؉ T-cell responses in the acute phase showed SIV control, whereas the remaining three with Nef-specific but not Vif-specific CD8 ؉ T-cell responses failed to control SIV replication. Analysis of 18 animals, consisting of seven unvaccinated noncontrollers and the 11 vaccinees described above, revealed that the sum of Gag-and Vifspecific CD8؉ T-cell frequencies in the acute phase was inversely correlated with plasma viral loads in the chronic phase. Our results suggest that replication of the AIDS virus can be controlled by vaccine-induced subdominant Gag/Vif epitope-specific CD8 ؉ T cells, providing a rationale for the induction of Gag-and/or Vif-specific CD8 ؉ T-cell responses by prophylactic AIDS vaccines.

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Section: Plasma Viral Loads After Sivmac239 Challengesupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Plasma Viral Loads After Sivmac239 Challengementioning

confidence: 92%

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Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 ⁺ T Cells

Iwamoto

Takahashi

Seki

et al. 2014

J Virol

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“…2) were performed using in total twelve Burmese rhesus macaques (Macaca mulatta) as shown in Table 1. We used three groups of rhesus macaques possessing the MHC-I haplotypes 90-010-Ie (E) (n = 6), 89-075-Iw (W) (n = 4), and 91-010-Is (S) (n = 2), respectively [35][36][37] . These twelve animals were intravenously inoculated with 1,000 50% tissue culture infective doses (TCID 50 ) of SIVmac239 38 .…”

Section: Animal Experiments Animal Experiments Were Carried Out In Tmentioning

confidence: 99%

“…These twelve animals were intravenously inoculated with 1,000 50% tissue culture infective doses (TCID 50 ) of SIVmac239 38 . Viral loads and T-cell responses pre-ART in macaques NE1, NE2, NW4, NS6, VE1, VE2, VW4, and VS6 were described before 36 . All of these macaques received ART from week 12 to 32 post-infection.…”

Section: Animal Experiments Animal Experiments Were Carried Out In Tmentioning

confidence: 99%

Therapeutic vaccine-mediated Gag-specific CD8+ T-cell induction under anti-retroviral therapy augments anti-virus efficacy of CD8+ cells in simian immunodeficiency virus-infected macaques

Nakamura-Hoshi

Takahara

Matsuoka

et al. 2020

Sci Rep

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Anti-retroviral therapy (ART) can inhibit HIV proliferation but not achieve virus eradication from HIV-infected individuals. Under ART-based HIV control, virus-specific CD8 + t-cell responses are often reduced. Here, we investigated the impact of therapeutic vaccination inducing virus-specific CD8 + T-cell responses under ART on viral control in a macaque AIDS model. Twelve rhesus macaques received ART from week 12 to 32 after simian immunodeficiency virus (SIV) infection. Six of them were vaccinated with Sendai virus vectors expressing SIV Gag and Vif at weeks 26 and 32, and Gag/ Vif-specific CD8 + T-cell responses were enhanced and became predominant. All macaques controlled viremia during ART but showed viremia rebound after ART cessation. Analysis of in vitro CD8 + cell ability to suppress replication of autologous lymphocytes-derived SIVs found augmentation of anti-SIV efficacy of CD8 + cells after vaccination. In the vaccinated animals, the anti-SIV efficacy of CD8 + cells at week 34 was correlated positively with Gag-specific CD8 + T-cell frequencies and inversely with rebound viral loads at week 34. These results indicate that Gag-specific CD8 + t-cell induction by therapeutic vaccination can augment anti-virus efficacy of CD8 + cells, which may be insufficient for functional cure but contribute to more stable viral control under ART. HIV induces persistent infection leading to AIDS onset in humans. Anti-retroviral therapy (ART) can control HIV replication and prevent AIDS progression. However, ART is unable to eradicate viruses and HIV-infected individuals need to receive lifelong therapy for AIDS prevention 1-4. It has been suggested that ART does not always exhibit complete shutdown of viral replication, while blips of undetectable levels of viral replication under ART may cause chronic persistent inflammation, possibly leading to progression of aging-related diseases 5-9. Virus-specific cytotoxic CD8 + T-cell responses play a central role in the control of HIV and simian immunodeficiency virus (SIV) replication 10-14. Because ART-based HIV control is often accompanied by reduced virusspecific CD8 + T-cell responses 15,16 , augmentation of effective CD8 + T-cell responses by therapeutic vaccination

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Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques

et al. 2015

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Immune pressure exerted by MHC class I-restricted cytotoxic T cells drives the development of viral escape mutations, thereby regulating HIV disease progression. Nonetheless, the relationship between host immunity and HIV central nervous system (CNS) disease remains poorly understood. The simian immunodeficiency virus (SIV) macaque model recapitulates key features of HIV infection including development of AIDS and CNS disease. To investigate cell-mediated immunity regulating SIV CNS disease progression, we compared the incidence of SIV encephalitis and the influence of MHC class I allele expression on the development of CNS disease in rhesus macaques (Macaca mulatta) versus pigtailed macaques (Macaca nemestrina). After inoculation with the immunosuppressive swarm SIV/DeltaB670 and the neurovirulent molecular clone SIV/17E-Fr, pigtailed macaques progressed more rapidly to AIDS, had higher plasma and cerebrospinal fluid (CSF) viral loads, and were more likely to progress to SIV-associated encephalitis (SIVE) compared to rhesus macaques. In addition, MHC class I alleles were neuroprotective in both species (Mamu-A*001 in rhesus macaques and Mane-A1*084:01:01 in pigtailed macaques); animals expressing these alleles were less likely to develop SIV encephalitis and correspondingly had lower viral replication in the brain. Species-specific differences in susceptibility to SIV disease demonstrated that cell mediated immune responses are critical to SIV CNS disease progression.

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Major histocompatibility complex class I-restricted cytotoxic T lymphocyte responses during primary simian immunodeficiency virus infection in Burmese rhesus macaques

Abstract: Major histocompatibility complex class I (MHC-I)-restricted CD8Key words cytotoxic T lymphocyte, human immunodeficiency virus, major histocompatibility complex, simian immunodeficiency virus.

Cited by 4 publications

References 24 publications

Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 ⁺ T Cells

Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 ⁺ T Cells

Therapeutic vaccine-mediated Gag-specific CD8+ T-cell induction under anti-retroviral therapy augments anti-virus efficacy of CD8+ cells in simian immunodeficiency virus-infected macaques

Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques

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Major histocompatibility complex class I-restricted cytotoxic T lymphocyte responses during primary simian immunodeficiency virus infection in Burmese rhesus macaques

Abstract: Major histocompatibility complex class I (MHC-I)-restricted CD8Key words cytotoxic T lymphocyte, human immunodeficiency virus, major histocompatibility complex, simian immunodeficiency virus.

Cited by 4 publications

References 24 publications

Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 + T Cells

Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 + T Cells

Therapeutic vaccine-mediated Gag-specific CD8+ T-cell induction under anti-retroviral therapy augments anti-virus efficacy of CD8+ cells in simian immunodeficiency virus-infected macaques

Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques

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Product

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Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 ⁺ T Cells

Control of Simian Immunodeficiency Virus Replication by Vaccine-Induced Gag- and Vif-Specific CD8 ⁺ T Cells