Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques

Alexandra M. Ortiz, Nichole Klatt, Bing Li, Yanjie Yi, Brian Tabb, Xing Pei Hao, Lawrence Sternberg, Benton Lawson, Paul M. Carnathan, Elizabeth M. Cramer, Jessica C. Engram, Dawn M. Little, Elena Ryzhova, Francisco Gonzalez-Scarano, Mirko Paiardini, Aftab A. Ansari, Sarah Ratcliffe, James G. Else, Jason M. Brenchley, Ronald G. CollmanJacob D. Estes, Cynthia A. Derdeyn, Guido Silvestri

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte - depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell - mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.

Original languageEnglish (US)
Pages (from-to)4433-4445
Number of pages13
JournalJournal of Clinical Investigation
Volume121
Issue number11
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Fingerprint

Viremia
Macaca mulatta
Virus Replication
T-Lymphocytes
Antiviral Agents
Disease Progression
AIDS Vaccines
Infection
Primates
HIV Infections
Acquired Immunodeficiency Syndrome
B-Lymphocytes
HIV
Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques. / Ortiz, Alexandra M.; Klatt, Nichole; Li, Bing; Yi, Yanjie; Tabb, Brian; Hao, Xing Pei; Sternberg, Lawrence; Lawson, Benton; Carnathan, Paul M.; Cramer, Elizabeth M.; Engram, Jessica C.; Little, Dawn M.; Ryzhova, Elena; Gonzalez-Scarano, Francisco; Paiardini, Mirko; Ansari, Aftab A.; Ratcliffe, Sarah; Else, James G.; Brenchley, Jason M.; Collman, Ronald G.; Estes, Jacob D.; Derdeyn, Cynthia A.; Silvestri, Guido.

In: Journal of Clinical Investigation, Vol. 121, No. 11, 01.11.2011, p. 4433-4445.

Research output: Contribution to journalArticle

Ortiz, AM, Klatt, N, Li, B, Yi, Y, Tabb, B, Hao, XP, Sternberg, L, Lawson, B, Carnathan, PM, Cramer, EM, Engram, JC, Little, DM, Ryzhova, E, Gonzalez-Scarano, F, Paiardini, M, Ansari, AA, Ratcliffe, S, Else, JG, Brenchley, JM, Collman, RG, Estes, JD, Derdeyn, CA & Silvestri, G 2011, 'Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques', Journal of Clinical Investigation, vol. 121, no. 11, pp. 4433-4445. https://doi.org/10.1172/JCI46023
Ortiz, Alexandra M. ; Klatt, Nichole ; Li, Bing ; Yi, Yanjie ; Tabb, Brian ; Hao, Xing Pei ; Sternberg, Lawrence ; Lawson, Benton ; Carnathan, Paul M. ; Cramer, Elizabeth M. ; Engram, Jessica C. ; Little, Dawn M. ; Ryzhova, Elena ; Gonzalez-Scarano, Francisco ; Paiardini, Mirko ; Ansari, Aftab A. ; Ratcliffe, Sarah ; Else, James G. ; Brenchley, Jason M. ; Collman, Ronald G. ; Estes, Jacob D. ; Derdeyn, Cynthia A. ; Silvestri, Guido. / Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 11. pp. 4433-4445.
@article{0d730968b838492c9d1ff7cc8aa04cd0,
title = "Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques",
abstract = "CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte - depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell - mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.",
author = "Ortiz, {Alexandra M.} and Nichole Klatt and Bing Li and Yanjie Yi and Brian Tabb and Hao, {Xing Pei} and Lawrence Sternberg and Benton Lawson and Carnathan, {Paul M.} and Cramer, {Elizabeth M.} and Engram, {Jessica C.} and Little, {Dawn M.} and Elena Ryzhova and Francisco Gonzalez-Scarano and Mirko Paiardini and Ansari, {Aftab A.} and Sarah Ratcliffe and Else, {James G.} and Brenchley, {Jason M.} and Collman, {Ronald G.} and Estes, {Jacob D.} and Derdeyn, {Cynthia A.} and Guido Silvestri",
year = "2011",
month = "11",
day = "1",
doi = "10.1172/JCI46023",
language = "English (US)",
volume = "121",
pages = "4433--4445",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "11",

}

TY - JOUR

T1 - Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques

AU - Ortiz, Alexandra M.

AU - Klatt, Nichole

AU - Li, Bing

AU - Yi, Yanjie

AU - Tabb, Brian

AU - Hao, Xing Pei

AU - Sternberg, Lawrence

AU - Lawson, Benton

AU - Carnathan, Paul M.

AU - Cramer, Elizabeth M.

AU - Engram, Jessica C.

AU - Little, Dawn M.

AU - Ryzhova, Elena

AU - Gonzalez-Scarano, Francisco

AU - Paiardini, Mirko

AU - Ansari, Aftab A.

AU - Ratcliffe, Sarah

AU - Else, James G.

AU - Brenchley, Jason M.

AU - Collman, Ronald G.

AU - Estes, Jacob D.

AU - Derdeyn, Cynthia A.

AU - Silvestri, Guido

PY - 2011/11/1

Y1 - 2011/11/1

N2 - CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte - depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell - mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.

AB - CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte - depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell - mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.

UR - http://www.scopus.com/inward/record.url?scp=80555146755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80555146755&partnerID=8YFLogxK

U2 - 10.1172/JCI46023

DO - 10.1172/JCI46023

M3 - Article

C2 - 22005304

AN - SCOPUS:80555146755

VL - 121

SP - 4433

EP - 4445

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 11

ER -