Suppression of Human Immunodeficiency Virus Type 1 (HIV-1) Viremia with Reverse Transcriptase and Integrase Inhibitors, CD4+ T-Cell Recovery, and Viral Rebound upon Interruption of Therapy in a New Model for HIV Treatment in the Humanized Rag2-/-γc-/- Mouse

被引：60

作者：

Choudhary, Shailesh K. ^{[1
]}

Rezk, Naser L. ^{[2
]}

Ince, William L. ^{[3
]}

Cheema, Manzoor ^{[1
]}

Zhang, Liguo ^{[4
]}

Su, Lishan ^{[3
,4
]}

Swanstrom, Ronald ^{[3
]}

Kashuba, Angela D. M. ^{[2
]}

Margolis, David M. ^{[1
,4
,5
]}

机构：

[1] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA

来源：

JOURNAL OF VIROLOGY | 2009年 / 83卷 / 16期

关键词：

IN-VITRO; ANTIRETROVIRAL THERAPY; RHESUS MACAQUES; MICE; INFECTION; TRANSMISSION; TENOFOVIR; EMTRICITABINE; REPLICATION; RALTEGRAVIR;

D O I：

10.1128/JVI.00580-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A small animal model that reproduces human immunodeficiency virus type 1 (HIV-1) pathogenesis may allow modeling of new therapeutic strategies in ways not approachable in mononuclear cell culture. We find that, as in humans, combination antiretroviral therapy (ART) in humanized (hu-) Rag2(-/-)gamma(-/-)(c) mice allows suppression of viremia below the limits of detection and recovery of CD4(+) cells, while interruption of ART results in viral rebound and renewed loss of CD4(+) T cells. Failure of ART in infected mice is associated with the appearance of drug resistance mutations. The hu-Rag2(-/-)gamma(-/-)(c) mouse may therefore facilitate testing of novel approaches to HIV replication and persistence.

引用

页码：8254 / 8258

页数：5

共 23 条

[1] In vitro characterization of a simian immunodeficiency virus-human immunodeficiency virus (HIV) chimera expressing HIV type 1 reverse transcriptase to study antiviral resistance in pigtail macaques [J].

Ambrose, Z ;

Boltz, V ;

Palmer, S ;

Coffin, JM ;

Hughes, SH ;

KewalRamani, VN .

JOURNAL OF VIROLOGY, 2004, 78 (24) :13553-13561

[2] Suppression of viremia and evolution of human immunodeficiency virus type 1 drug resistance in a macaque model for Antiretroviral therapy [J].

Ambrose, Zandrea ;

Palmer, Sarah ;

Boltz, Valerie F. ;

Kearney, Mary ;

Larsen, Kay ;

Polacino, Patricia ;

Flanary, Leon ;

Oswald, Kelli ;

Piatak, Michael, Jr. ;

Smedley, Jerem ;

Shao, Wei ;

Bischofberger, Norbert ;

Maldarelli, Frank ;

Kimata, Jason T. ;

Mellors, John W. ;

Hu, Shiu-Lok ;

Coffin, John M. ;

Lifson, Jeffrey D. ;

KewalRamani, Vineet N. .

JOURNAL OF VIROLOGY, 2007, 81 (22) :12145-12155

[3] Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-γc-/- mice [J].

Baenziger, Stefan ;

Tussiwand, Roxane ;

Schlaepfer, Erika ;

Mazzucchelli, Luca ;

Heikenwalder, Mathias ;

Kurrer, Michael O. ;

Behnke, Silvia ;

Frey, Joachim ;

Oxenius, Annette ;

Joller, Helen ;

Aguzzi, Adriano ;

Manz, Markus G. ;

Speck, Roberto F. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (43) :15951-15956

[4] Mucosal transmission of R5 and X4 tropic HIV-1 via vaginal and rectal routes in humanized Rag-/- γc-/- (RAG-hu) mice [J].

Berges, Bradford K. ;

Akkina, Sarah R. ;

Folkvord, Joy M. ;

Connick, Elizabeth ;

Akkina, Ramesh .

VIROLOGY, 2008, 373 (02) :342-351

[5] HIV-1 infection and CD4 T cell depletion in the humanized Rag2-/-γc-/- (RAG-hu) mouse model [J].

Berges, Bradford K. ;

Wheat, William H. ;

Palmer, Brent E. ;

Connick, Elizabeth ;

Akkina, Ramesh .

RETROVIROLOGY, 2006, 3 (1)

[6] Steady-state pharmacokinetics of emtricitabine and tenofovir disoproxil fumarate administered alone and in combination in healthy volunteers [J].

Blum, M. Robert ;

Chittick, Gregory E. ;

Begley, John A. ;

Zong, Jian .

JOURNAL OF CLINICAL PHARMACOLOGY, 2007, 47 (06) :751-759

[7] Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice [J].

Denton, Paul W. ;

Estes, Jacob D. ;

Sun, Zhifeng ;

Othieno, Florence A. ;

Wei, Bangdong L. ;

Wege, Anja K. ;

Powell, Daniel A. ;

Payne, Deborah ;

Haase, Ashley T. ;

Garcia, J. Victor .

PLOS MEDICINE, 2008, 5 (01) :79-89

[8] IDENTIFICATION OF CONSERVED AMINO-ACID-RESIDUES CRITICAL FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE FUNCTION-INVITRO [J].

ENGELMAN, A ;

CRAIGIE, R .

JOURNAL OF VIROLOGY, 1992, 66 (11) :6361-6369

[9] Effects of mutations in residues near the active site of human immunodeficiency virus type 1 integrase on specific enzyme-substrate interactions [J].

Gerton, JL ;

Ohgi, S ;

Olsen, M ;

Derisi, J ;

Brown, PO .

JOURNAL OF VIROLOGY, 1998, 72 (06) :5046-5055

[10] Antiretroviral treatment of adult HIV infection - 2008 recommendations of the International AIDS Society USA panel [J].

Hammer, Scott M. ;

Eron, Joseph J., Jr. ;

Reiss, Peter ;

Schooley, Robert T. ;

Thompson, Melanie A. ;

Walmsley, Sharon ;

Cahn, Pedro ;

Fischl, Margaret A. ;

Gatell, Jose M. ;

Hirsch, Martin S. ;

Jacobsen, Donna M. ;

Montaner, Julio S. G. ;

Richman, Douglas D. ;

Yeni, Patrick G. ;

Volberding, Paul A. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 300 (05) :555-570

← 1 2 3 →