Erratum: Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques

Baba, Timothy W.; Liška, Vladimír; Khimani, Anis H.; Ray, Nancy B.; Dailey, P.J.; Penninck, D.; Bronson, R.; Greene, M.F.; McClure, Harold M.; Martin, Louis N.; Ruprecht, R. M.

doi:10.1038/8859

Cited by 183 publications

(88 citation statements)

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“…For instance, whereas AIDS vaccines based on a live-attenuated virus have shown promise in the SIVmacaque model, virus evolution studies revealed that such vaccines will likely be unsafe (Johnson & Desrosiers 1998;Mills et al 2000;Whitney & Ruprecht 2004;Koff et al 2006). The major safety concern is that a chronic infection is established and low-level replication of the attenuated virus may eventually lead to the selection of fitter and pathogenic virus variants (Baba et al 1995(Baba et al , 1999Whatmore et al 1995;Chakrabarti et al 2003;HofmannLehmann et al 2003). The D3 HIV-1 variant, which is attenuated by deletions in three non-essential genome segments, was considered a vaccine candidate because it seemed impossible that the virus could evolve to a pathogenic variant through repair of the deletions.…”

Section: Evolution Of Hiv-1 Vaccinesmentioning

confidence: 99%

HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms

Das

Berkhout

2010

Phil. Trans. R. Soc. B

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Replication of HIV-1 under selective pressure frequently results in the evolution of virus variants that replicate more efficiently under the applied conditions. For example, in patients on antiretroviral therapy, such evolution can result in variants that are resistant to the HIV-1 inhibitors, thus frustrating the therapy. On the other hand, virus evolution can help us to understand the molecular mechanisms that underlie HIV-1 replication. For example, evolution of a defective virus mutant can result in variants that overcome the introduced defect by restoration of the original sequence or by the introduction of additional mutations in the viral genome. Analysis of the evolution pathway can reveal the requirements of the element under study and help to understand its function. Analysis of the escape routes may generate new insight in the viral life cycle and result in the identification of unexpected biological mechanisms. We have developed in vitro HIV-1 evolution into a systematic research tool that allows the study of different aspects of the viral replication cycle. We will briefly review this method of forced virus evolution and provide several examples that illustrate the power of this approach.

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Section: Evolution Of Hiv-1 Vaccinesmentioning

confidence: 99%

HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms

Das

Berkhout

2010

Phil. Trans. R. Soc. B

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“…[6][7][8] Rhesus macaques infected with nef-defective molecular clones of simian immunodeficiency virus (SIV) also exhibit significant reductions in pathogenicity. 9 These animals exhibit extended periods of asymptomatic disease, but eventually progress to simian AIDS much like their human counterparts. 9 Interestingly, neftransgenic mice suffer organ system dysfunction and severe CD4 þ T cell depletion similar to AIDS patients.…”

Section: Introductionmentioning

confidence: 99%

“…9 These animals exhibit extended periods of asymptomatic disease, but eventually progress to simian AIDS much like their human counterparts. 9 Interestingly, neftransgenic mice suffer organ system dysfunction and severe CD4 þ T cell depletion similar to AIDS patients. [10][11][12][13] Taken together these studies provide evidence that HIV-1 Nef plays a central role in the pathogenesis leading to AIDS.…”

Section: Introductionmentioning

confidence: 99%

HIV Type 1 Nef Is Released from Infected Cells in CD45⁺Microvesicles and Is Present in the Plasma of HIV-Infected Individuals

Raymond

Campbell-Sims²,

Khan³

et al. 2011

AIDS Research and Human Retroviruses

148

157

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HIV-1 Nef has been demonstrated to be integral for viral persistence, infectivity, and the acceleration of disease pathogenesis (AIDS) in humans. Nef has also been detected in the plasma of HIV-infected individuals and is released from infected cells. The form in which Nef is released from infected cells is unknown. However, Nef is a myristoylated protein and has been shown to interact with the intracellular vesicular trafficking network. Here we show that Nef is released in CD45-containing microvesicles. This microvesicular Nef (mvNef) is detected in the plasma of HIV-infected individuals at relatively high concentrations (10 ng/ml). It is also present in tissue culture supernatants of Jurkat cells infected with HIV MN . Interestingly, plasma mvNef levels in HIV þ patients did not significantly correlate with viral load or CD4 count. Microvesicular Nef levels persisted in the plasma of HIVinfected individuals despite the use of antiretroviral therapy, even in individuals with undetectable viral loads. Using cell lines, we found Nef microvesicles induce apoptosis in Jurkat T-lymphocytes but had no observed effect on the U937 monocytic cell line. Given the large amount of mvNef present in the plasma of HIV-infected individuals, the apoptotic effect of mvNef on T cells, and the observed functions of extracellular soluble Nef in vitro, it seems likely that in vivo mvNef may play a significant role in the pathogenesis of AIDS.

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“…Because of the safety concerns and inadequate protection of the more attenuated liveattenuated vaccine, the vaccine field is currently not actively pursuing live-attenuated vaccines for use in humans. 1,4,6,[27][28][29][30] Previously, the efficacy of various Adand MVA-based vaccines about the susceptibility to SHIV infection in monkeys has been examined by our research group and other scientists. 10,24 This study investigates whether a combination of these vaccines can prevent SIV infection.…”

Section: Discussionmentioning

confidence: 99%

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Kondo

Yoshida

et al. 2009

Gene Ther

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This study explores the effect of priming rhesus monkeys with an Ad5/35 vector expressing simian immunodeficiency virus (SIV) gag and gp120, and then boosting the animals with an modified vaccinia virus Ankara (MVA) vector encoding the same antigens after a 2-month interval. The animals were intravenously challenged with 100 TCID50 of highly pathogenic SIVmac239 virus 2 months after the booster vaccination. The priming vaccination induced robust SIV-specific cell-mediated and humoral immune responses, and boosting further enhanced the cellular immunity. Vaccination reduced peak and long-term viral loads by 1-2 logs for a period of 46 months, as reflected by a reduction in both the SIV RNA and DNA levels. Of considerable interest, the immunized monkeys did not suffer from loss of CD4 T cells, particularly central memory CD4 T cells. These results demonstrate that prophylactic vaccination with Ad5/35 followed by MVA reduces viral replication and prevents CD4 T-cell loss, and that these effects may decrease the likelihood of disease progression.

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Erratum: Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques

Cited by 183 publications

References 0 publications

HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms

HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms

HIV Type 1 Nef Is Released from Infected Cells in CD45⁺Microvesicles and Is Present in the Plasma of HIV-Infected Individuals

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

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Erratum: Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques

Cited by 183 publications

References 0 publications

HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms

HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms

HIV Type 1 Nef Is Released from Infected Cells in CD45+Microvesicles and Is Present in the Plasma of HIV-Infected Individuals

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

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HIV Type 1 Nef Is Released from Infected Cells in CD45⁺Microvesicles and Is Present in the Plasma of HIV-Infected Individuals