Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

M. Anthony Moody; Feng Gao; Thaddeus C. Gurley; Joshua D. Amos; Amit Kumar; Bhavna Hora; Dawn J. Marshall; John F. Whitesides; Shi Mao Xia; Robert Parks; Krissey E. Lloyd; Kwan Ki Hwang; Xiaozhi Lu; Mattia Bonsignori; Andrés Finzi; Nathan A. Vandergrift; S. Munir Alam; Guido Ferrari; Xiaoying Shen; Georgia D. Tomaras; Gift Kamanga; Myron S. Cohen; Noel E. Sam; Saidi Kapiga; Elin S. Gray; Nancy L. Tumba; Lynn Morris; Susan Zolla-Pazner; Miroslaw K. Gorny; John R. Mascola; Beatrice H. Hahn; George M. Shaw; Joseph G. Sodroski; Hua Xin Liao; David C. Montefiori; Peter T. Hraber; Bette T. Korber; Barton F. Haynes

doi:10.1016/j.chom.2015.08.006

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

M. Anthony Moody, Feng Gao, Thaddeus C. Gurley, Joshua D. Amos, Amit Kumar, Bhavna Hora, Dawn J. Marshall, John F. Whitesides, Shi Mao Xia, Robert Parks, Krissey E. Lloyd, Kwan Ki Hwang, Xiaozhi Lu, Mattia Bonsignori, Andrés Finzi, Nathan A. Vandergrift, S. Munir Alam, Guido Ferrari, Xiaoying Shen, Georgia D. TomarasGift Kamanga, Myron S. Cohen, Noel E. Sam, Saidi Kapiga, Elin S. Gray, Nancy L. Tumba, Lynn Morris, Susan Zolla-Pazner, Miroslaw K. Gorny, John R. Mascola, Beatrice H. Hahn, George M. Shaw, Joseph G. Sodroski, Hua Xin Liao, David C. Montefiori, Peter T. Hraber, Bette T. Korber, Barton F. Haynes

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Abstract

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

Original language	English
Pages (from-to)	354-362
Number of pages	9
Journal	Cell Host and Microbe
Volume	18
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2015.08.006
State	Published - 9 Sep 2015

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Moody, M. A., Gao, F., Gurley, T. C., Amos, J. D., Kumar, A., Hora, B., Marshall, D. J., Whitesides, J. F., Xia, S. M., Parks, R., Lloyd, K. E., Hwang, K. K., Lu, X., Bonsignori, M., Finzi, A., Vandergrift, N. A., Alam, S. M., Ferrari, G., Shen, X., ... Haynes, B. F. (2015). Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host and Microbe, 18(3), 354-362. https://doi.org/10.1016/j.chom.2015.08.006

@article{af6015b85bcf4a76a7dc3355f9cf5e93,

title = "Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses",

abstract = "The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.",

author = "Moody, {M. Anthony} and Feng Gao and Gurley, {Thaddeus C.} and Amos, {Joshua D.} and Amit Kumar and Bhavna Hora and Marshall, {Dawn J.} and Whitesides, {John F.} and Xia, {Shi Mao} and Robert Parks and Lloyd, {Krissey E.} and Hwang, {Kwan Ki} and Xiaozhi Lu and Mattia Bonsignori and Andr{\'e}s Finzi and Vandergrift, {Nathan A.} and Alam, {S. Munir} and Guido Ferrari and Xiaoying Shen and Tomaras, {Georgia D.} and Gift Kamanga and Cohen, {Myron S.} and Sam, {Noel E.} and Saidi Kapiga and Gray, {Elin S.} and Tumba, {Nancy L.} and Lynn Morris and Susan Zolla-Pazner and Gorny, {Miroslaw K.} and Mascola, {John R.} and Hahn, {Beatrice H.} and Shaw, {George M.} and Sodroski, {Joseph G.} and Liao, {Hua Xin} and Montefiori, {David C.} and Hraber, {Peter T.} and Korber, {Bette T.} and Haynes, {Barton F.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = sep,

day = "9",

doi = "10.1016/j.chom.2015.08.006",

language = "English",

volume = "18",

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Moody, MA, Gao, F, Gurley, TC, Amos, JD, Kumar, A, Hora, B, Marshall, DJ, Whitesides, JF, Xia, SM, Parks, R, Lloyd, KE, Hwang, KK, Lu, X, Bonsignori, M, Finzi, A, Vandergrift, NA, Alam, SM, Ferrari, G, Shen, X, Tomaras, GD, Kamanga, G, Cohen, MS, Sam, NE, Kapiga, S, Gray, ES, Tumba, NL, Morris, L, Zolla-Pazner, S, Gorny, MK, Mascola, JR, Hahn, BH, Shaw, GM, Sodroski, JG, Liao, HX, Montefiori, DC, Hraber, PT, Korber, BT & Haynes, BF 2015, 'Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses', Cell Host and Microbe, vol. 18, no. 3, pp. 354-362. https://doi.org/10.1016/j.chom.2015.08.006

TY - JOUR

T1 - Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

AU - Moody, M. Anthony

AU - Gao, Feng

AU - Gurley, Thaddeus C.

AU - Amos, Joshua D.

AU - Kumar, Amit

AU - Hora, Bhavna

AU - Marshall, Dawn J.

AU - Whitesides, John F.

AU - Xia, Shi Mao

AU - Parks, Robert

AU - Lloyd, Krissey E.

AU - Hwang, Kwan Ki

AU - Lu, Xiaozhi

AU - Bonsignori, Mattia

AU - Finzi, Andrés

AU - Vandergrift, Nathan A.

AU - Alam, S. Munir

AU - Ferrari, Guido

AU - Shen, Xiaoying

AU - Tomaras, Georgia D.

AU - Kamanga, Gift

AU - Cohen, Myron S.

AU - Sam, Noel E.

AU - Kapiga, Saidi

AU - Gray, Elin S.

AU - Tumba, Nancy L.

AU - Morris, Lynn

AU - Zolla-Pazner, Susan

AU - Gorny, Miroslaw K.

AU - Mascola, John R.

AU - Hahn, Beatrice H.

AU - Shaw, George M.

AU - Sodroski, Joseph G.

AU - Liao, Hua Xin

AU - Montefiori, David C.

AU - Hraber, Peter T.

AU - Korber, Bette T.

AU - Haynes, Barton F.

PY - 2015/9/9

Y1 - 2015/9/9

N2 - The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

AB - The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

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U2 - 10.1016/j.chom.2015.08.006

DO - 10.1016/j.chom.2015.08.006

M3 - Article

C2 - 26355218

AN - SCOPUS:84941285955

SN - 1931-3128

VL - 18

SP - 354

EP - 362

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

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