Replication competent virus as an important source of bias in HIV latency models utilizing single round viral constructs

Bonczkowski, Pawel; Spiegelaere, Ward De; Bosque, Alberto; White, Cory H.; Nuffel, Anouk Van; Malatinková, Eva; Kiselinova, Maja; Trypsteen, Wim; Witkowski, Wojciech; Vermeíre, Jolien; Verhasselt, Bruno; Martins, Laura J.; Woelk, Christopher H.; Planelles, Vicente; Vandekerckhove, Linos

doi:10.1186/s12977-014-0070-3

“…Compared to αCD3/αCD28-stimulated cells at 6 days postinfection, untreated resting CD4 + T cells showed significantly lower levels of HIV infection but, nonetheless, permitted both productive and latent infection ( Fig 1C ). Importantly, productive and latent infection of resting CD4 + T cells over the 6-day time-course was not the result of replication-competent virus being present in our HIV Duo-Fluo I viral stocks ( S2 Fig ) [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells

Chávez

¹

,

Calvanese

²

,

Verdin

³

2015

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Highly active antiretroviral therapy (HAART) suppresses human immunodeficiency virus (HIV) replication to undetectable levels but cannot fully eradicate the virus because a small reservoir of CD4+ T cells remains latently infected. Since HIV efficiently infects only activated CD4+ T cells and since latent HIV primarily resides in resting CD4+ T cells, it is generally assumed that latency is established when a productively infected cell recycles to a resting state, trapping the virus in a latent state. In this study, we use a dual reporter virus—HIV Duo-Fluo I, which identifies latently infected cells immediately after infection—to investigate how T cell activation affects the estab-lishment of HIV latency. We show that HIV latency can arise from the direct infection of both resting and activated CD4+ T cells. Importantly, returning productively infected cells to a resting state is not associated with a significant silencing of the integrated HIV. We further show that resting CD4+ T cells from human lymphoid tissue (tonsil, spleen) show increased latency after infection when compared to peripheral blood. Our findings raise significant questions regarding the most commonly accepted model for the establishment of latent HIV and suggest that infection of both resting and activated primary CD4+ T cells produce latency.

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“…Shaw (Keele et al, 2008), and HIV-1 AC10.29 Env Expression Vector (AC10.0, clone 29 (SVPB13)) from Dr. David Montefiori and Dr. Feng Gao (Li et al, 2005). pLET-LAI, pLET JRFL and DHIV plasmids were a kind gift from Vicente Planelles (Bonczkowski et al, 2014;Bosque and Planelles, 2009;Challita-Eid et al, 1998). The pCAGGS-JRFL and pcDNA(3)-BaL.01 were a kind gift from Paulo Lusso (Guzzo et al, 2018).…”

Section: Molecular Clonesmentioning

confidence: 99%

Sensitivity to monoclonal antibody 447-52D and an open env trimer conformation correlate poorly with inhibition of HIV-1 infectivity by SERINC5

Angerstein

¹

,

Stoneham

²

,

Ramirez

³

et al. 2020

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The host protein SERINC5 inhibits the infectivity of HIV-1 virions in an Env-dependent manner and is counteracted by Nef. The conformation of the Env trimer reportedly correlates with sensitivity to SERINC5.Here, we tested the hypothesis that the "open" conformation of the Env trimer revealed by sensitivity to the V3-loop specific antibody 447-52D directly correlates with sensitivity to SERINC5. Of five Envs tested, SF162 was the most sensitive to neutralization by 447-52D, but it was not the most sensitive to SERINC5; instead the Env of LAI was substantially more sensitive to SERINC5 than all the other Envs. Mutational opening of the trimer by substitution of two tyrosines that mediate interaction between the V2 and V3 loops sensitized the Envs of JRFL and LAI to 447-52D as previously reported, but only BaL was sensitized to SERINC5. These data suggest that trimer "openness" is not sufficient for sensitivity to SERINC5.

show abstract

“…Shaw (Keele et al, 2008), and HIV-1 AC10.29 Env Expression Vector (AC10.0, clone 29 (SVPB13)) from Dr. David Montefiori and Dr. Feng Gao (Li et al, 2005). pLET-LAI, pLET JRFL and DHIV plasmids were a kind gift from Vicente Planelles (Bonczkowski et al, 2014;Bosque and Planelles, 2009;Challita-Eid et al, 1998). The pCAGGS-JRFL and pcDNA(3)-BaL.01 were a kind gift from Paulo Lusso (Guzzo et al, 2018).…”

Section: Molecular Clonesmentioning

confidence: 99%

Sensitivity to Monoclonal Antibody 447-52D and an Open Env Trimer Conformation Correlate Poorly with Inhibition of HIV-1 Infectivity by SERINC5

Angerstein

¹

,

Stoneham

²

,

Ramirez

³

et al. 2020

Preprint

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The host protein SERINC5 inhibits the infectivity of HIV-1 virions in an Env-dependent manner and is counteracted by Nef. The conformation of the Env trimer reportedly correlates with sensitivity to SERINC5.Here, we tested the hypothesis that the "open" conformation of the Env trimer revealed by sensitivity to the V3-loop specific antibody 447-52D directly correlates with sensitivity to SERINC5. Of five Envs tested, SF162 was the most sensitive to neutralization by 447-52D, but it was not the most sensitive to SERINC5; instead the Env of LAI was substantially more sensitive to SERINC5 than all the other Envs. Mutational opening of the trimer by substitution of two tyrosines that mediate interaction between the V2 and V3 loops sensitized the Envs of JRFL and LAI to 447-52D as previously reported, but only BaL was sensitized to SERINC5. These data suggest that trimer "openness" is not sufficient for sensitivity to SERINC5.

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Replication competent virus as an important source of bias in HIV latency models utilizing single round viral constructs

Cited by 8 publications

References 14 publications

HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells

HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells

Sensitivity to monoclonal antibody 447-52D and an open env trimer conformation correlate poorly with inhibition of HIV-1 infectivity by SERINC5

Sensitivity to Monoclonal Antibody 447-52D and an Open Env Trimer Conformation Correlate Poorly with Inhibition of HIV-1 Infectivity by SERINC5

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