Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins

Gregory Q. Del Prete; Braiden Ailers; Brian Moldt; Brandon F. Keele; Jacob D. Estes; Anthony Rodriguez; Marissa Sampias; Kelli Oswald; Randy Fast; Charles M. Trubey; Elena Chertova; Jeremy Smedley; Celia C. Labranche; David C. Montefiori; Dennis R. Burton; George M. Shaw; Marty Markowitz; Michael Piatak; Vineet N. Kewalramani; Paul D. Bieniasz; Jeffrey D. Lifson; Theodora Hatziioannou

doi:10.1016/j.chom.2014.08.003

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins

Gregory Q. Del Prete, Braiden Ailers, Brian Moldt, Brandon F. Keele, Jacob D. Estes, Anthony Rodriguez, Marissa Sampias, Kelli Oswald, Randy Fast, Charles M. Trubey, Elena Chertova, Jeremy Smedley, Celia C. Labranche, David C. Montefiori, Dennis R. Burton, George M. Shaw, Marty Markowitz, Michael Piatak, Vineet N. Kewalramani, Paul D. BieniaszJeffrey D. Lifson, Theodora Hatziioannou

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

42 Scopus citations

Abstract

Infection of macaques with chimeric viruses based on SIV_MAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.

Original language	English (US)
Pages (from-to)	412-418
Number of pages	7
Journal	Cell Host and Microbe
Volume	16
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2014.08.003
State	Published - Sep 10 2014
Externally published	Yes

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

Access to Document

10.1016/j.chom.2014.08.003

Cite this

Del Prete, G. Q., Ailers, B., Moldt, B., Keele, B. F., Estes, J. D., Rodriguez, A., Sampias, M., Oswald, K., Fast, R., Trubey, C. M., Chertova, E., Smedley, J., Labranche, C. C., Montefiori, D. C., Burton, D. R., Shaw, G. M., Markowitz, M., Piatak, M., Kewalramani, V. N., ... Hatziioannou, T. (2014). Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins. Cell Host and Microbe, 16(3), 412-418. https://doi.org/10.1016/j.chom.2014.08.003

Del Prete, GQ, Ailers, B, Moldt, B, Keele, BF, Estes, JD, Rodriguez, A, Sampias, M, Oswald, K, Fast, R, Trubey, CM, Chertova, E, Smedley, J, Labranche, CC, Montefiori, DC, Burton, DR, Shaw, GM, Markowitz, M, Piatak, M, Kewalramani, VN, Bieniasz, PD, Lifson, JD & Hatziioannou, T 2014, 'Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins', Cell Host and Microbe, vol. 16, no. 3, pp. 412-418. https://doi.org/10.1016/j.chom.2014.08.003

@article{0b3680c79cec45e7a77862366e993c0a,

title = "Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins",

abstract = "Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.",

author = "{Del Prete}, {Gregory Q.} and Braiden Ailers and Brian Moldt and Keele, {Brandon F.} and Estes, {Jacob D.} and Anthony Rodriguez and Marissa Sampias and Kelli Oswald and Randy Fast and Trubey, {Charles M.} and Elena Chertova and Jeremy Smedley and Labranche, {Celia C.} and Montefiori, {David C.} and Burton, {Dennis R.} and Shaw, {George M.} and Marty Markowitz and Michael Piatak and Kewalramani, {Vineet N.} and Bieniasz, {Paul D.} and Lifson, {Jeffrey D.} and Theodora Hatziioannou",

note = "Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",

year = "2014",

month = sep,

day = "10",

doi = "10.1016/j.chom.2014.08.003",

language = "English (US)",

volume = "16",

pages = "412--418",

journal = "Cell Host and Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins

AU - Del Prete, Gregory Q.

AU - Ailers, Braiden

AU - Moldt, Brian

AU - Keele, Brandon F.

AU - Estes, Jacob D.

AU - Rodriguez, Anthony

AU - Sampias, Marissa

AU - Oswald, Kelli

AU - Fast, Randy

AU - Trubey, Charles M.

AU - Chertova, Elena

AU - Smedley, Jeremy

AU - Labranche, Celia C.

AU - Montefiori, David C.

AU - Burton, Dennis R.

AU - Shaw, George M.

AU - Markowitz, Marty

AU - Piatak, Michael

AU - Kewalramani, Vineet N.

AU - Bieniasz, Paul D.

AU - Lifson, Jeffrey D.

AU - Hatziioannou, Theodora

PY - 2014/9/10

Y1 - 2014/9/10

N2 - Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.

AB - Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.

UR - http://www.scopus.com/inward/record.url?scp=84907693726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907693726&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2014.08.003

DO - 10.1016/j.chom.2014.08.003

M3 - Article

C2 - 25211081

AN - SCOPUS:84907693726

SN - 1931-3128

VL - 16

SP - 412

EP - 418

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this