HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing

Danielle E. Lyons; Priti Kumar; Nadia R. Roan; Patricia A. Defechereux; Cedric Feschotte; Ulrike C. Lange; Niren Murthy; Pauline Sameshima; Eric Verdin; Julie A. Ake; Matthew S. Parsons; Avindra Nath; Sara Gianella; Davey M. Smith; Esper G. Kallas; Thomas J. Villa; Richard Strange; Betty Mwesigwa; Robert L. Furler O’Brien; Douglas F. Nixon; Lishomwa C. Ndhlovu; Susana T. Valente; Melanie Ott

doi:10.3390/v15112171

HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing

Danielle E. Lyons, Priti Kumar, Nadia R. Roan, Patricia A. Defechereux, Cedric Feschotte, Ulrike C. Lange, Niren Murthy, Pauline Sameshima, Eric Verdin, Julie A. Ake, Matthew S. Parsons, Avindra Nath, Sara Gianella, Davey M. Smith, Esper G. Kallas, Thomas J. Villa, Richard Strange, Betty Mwesigwa, Robert L. Furler O’Brien, Douglas F. NixonLishomwa C. Ndhlovu^*, Susana T. Valente^*, Melanie Ott^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel “block-lock-stop” approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

Original language	English
Article number	2171
Journal	Viruses
Volume	15
Issue number	11
DOIs	https://doi.org/10.3390/v15112171
State	Published - Nov 2023
Externally published	Yes

Keywords

HERV
HIV-1 cure
latency
transcriptional silencing

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10.3390/v15112171

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Lyons, D. E., Kumar, P., Roan, N. R., Defechereux, P. A., Feschotte, C., Lange, U. C., Murthy, N., Sameshima, P., Verdin, E., Ake, J. A., Parsons, M. S., Nath, A., Gianella, S., Smith, D. M., Kallas, E. G., Villa, T. J., Strange, R., Mwesigwa, B., Furler O’Brien, R. L., ... Ott, M. (2023). HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing. Viruses, 15(11), Article 2171. https://doi.org/10.3390/v15112171

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title = "HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing",

abstract = "Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel “block-lock-stop” approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.",

keywords = "HERV, HIV-1 cure, latency, transcriptional silencing",

author = "Lyons, {Danielle E.} and Priti Kumar and Roan, {Nadia R.} and Defechereux, {Patricia A.} and Cedric Feschotte and Lange, {Ulrike C.} and Niren Murthy and Pauline Sameshima and Eric Verdin and Ake, {Julie A.} and Parsons, {Matthew S.} and Avindra Nath and Sara Gianella and Smith, {Davey M.} and Kallas, {Esper G.} and Villa, {Thomas J.} and Richard Strange and Betty Mwesigwa and {Furler O{\textquoteright}Brien}, {Robert L.} and Nixon, {Douglas F.} and Ndhlovu, {Lishomwa C.} and Valente, {Susana T.} and Melanie Ott",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = nov,

doi = "10.3390/v15112171",

language = "English",

volume = "15",

journal = "Viruses",

issn = "1999-4915",

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Lyons, DE, Kumar, P, Roan, NR, Defechereux, PA, Feschotte, C, Lange, UC, Murthy, N, Sameshima, P, Verdin, E, Ake, JA, Parsons, MS, Nath, A, Gianella, S, Smith, DM, Kallas, EG, Villa, TJ, Strange, R, Mwesigwa, B, Furler O’Brien, RL, Nixon, DF, Ndhlovu, LC, Valente, ST & Ott, M 2023, 'HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing', Viruses, vol. 15, no. 11, 2171. https://doi.org/10.3390/v15112171

TY - JOUR

T1 - HIV-1 Remission

T2 - Accelerating the Path to Permanent HIV-1 Silencing

AU - Lyons, Danielle E.

AU - Kumar, Priti

AU - Roan, Nadia R.

AU - Defechereux, Patricia A.

AU - Feschotte, Cedric

AU - Lange, Ulrike C.

AU - Murthy, Niren

AU - Sameshima, Pauline

AU - Verdin, Eric

AU - Ake, Julie A.

AU - Parsons, Matthew S.

AU - Nath, Avindra

AU - Gianella, Sara

AU - Smith, Davey M.

AU - Kallas, Esper G.

AU - Villa, Thomas J.

AU - Strange, Richard

AU - Mwesigwa, Betty

AU - Furler O’Brien, Robert L.

AU - Nixon, Douglas F.

AU - Ndhlovu, Lishomwa C.

AU - Valente, Susana T.

AU - Ott, Melanie

PY - 2023/11

Y1 - 2023/11

N2 - Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel “block-lock-stop” approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

AB - Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel “block-lock-stop” approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

KW - HERV

KW - HIV-1 cure

KW - latency

KW - transcriptional silencing

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U2 - 10.3390/v15112171

DO - 10.3390/v15112171

M3 - Article

C2 - 38005849

AN - SCOPUS:85177795275

SN - 1999-4915

VL - 15

JO - Viruses

JF - Viruses

IS - 11

M1 - 2171

ER -

HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing

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Keywords

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