HIV-1 Subtype C Phylodynamics in the Global Epidemic

被引:19
作者
Novitsky, Vlad [1 ,2 ]
Wang, Rui [3 ]
Lagakos, Stephen [3 ]
Essex, Max [1 ,2 ]
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, AIDS Initiat, Boston, MA 02115 USA
[2] Botswana Harvard AIDS Inst, Gaborone, Botswana
[3] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
来源
VIRUSES-BASEL | 2010年 / 2卷 / 01期
关键词
HIV-1 subtype C; consensus sequence; amino acid frequency; Gag; gag phylogeny; CTL epitopes; time of MRCA; T-CELL RESPONSES; VIRAL LOAD; GAG; CD8(+); SEQUENCE; ESCAPE; ASSOCIATION; SUBCLUSTER; PROTEINS; ETHIOPIA;
D O I
10.3390/v2010033
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and dynamic patterns of transmission of HIV lead to an even more complex population viral diversity over time, thus presenting enormous challenges to vaccine development. To address inter-patient viral evolution over time, a set of 653 unique HIV-1 subtype C gag sequences were retrieved from the LANL HIV Database, grouped by sampling year as <2000, 2000, 2001-2002, 2003, and 2004-2006, and analyzed for the site-specific frequency of translated amino acid residues. Phylogenetic analysis revealed that a total of 289 out of 653 (44.3%) analyzed sequences were found within 16 clusters defined by aLRT of more than 0.90. Median (IQR) inter-sample diversity of analyzed gag sequences was 8.7% (7.7%; 9.8%). Despite the heterogeneous origins of analyzed sequences, the gamut and frequency of amino acid residues in wild-type Gag were remarkably stable over the last decade of the HIV-1 subtype C epidemic. The vast majority of amino acid residues demonstrated minor frequency fluctuation over time, consistent with the conservative nature of the HIV-1 Gag protein. Only 4.0% (20 out of 500; HXB2 numbering) amino acid residues across Gag displayed both statistically significant (p<0.05 by both a trend test and heterogeneity test) changes in amino acid frequency over time as well as a range of at least 10% in the frequency of the major amino acid. A total of 59.2% of amino acid residues with changing frequency of 10%+ were found within previously identified CTL epitopes. The time of the most recent common ancestor of the HIV-1 subtype C was dated to around 1950 (95% HPD from 1928 to 1962). This study provides evidence for the overall stability of HIV-1 subtype C Gag among viruses circulating in the epidemic over the last decade. However selected sites across HIV-1C Gag with changing amino acid frequency are likely to be under selection pressure at the population level.
引用
收藏
页码:33 / 54
页数:22
相关论文
共 59 条
[31]   CD8+ T-cell responses to different HIV proteins have discordant associations with viral load [J].
Kiepiela, Photini ;
Ngumbela, Kholiswa ;
Thobakgale, Christina ;
Ramduth, Dhanwanthie ;
Honeyborne, Isobella ;
Moodley, Eshia ;
Reddy, Shabashini ;
de Pierres, Chantal ;
Mncube, Zenele ;
Mkhwanazi, Nompumelelo ;
Bishop, Karen ;
van der Stok, Mary ;
Nair, Kriebashnie ;
Khan, Nasreen ;
Crawford, Hayley ;
Payne, Rebecca ;
Leslie, Alasdair ;
Prado, Julia ;
Prendergast, Andrew ;
Frater, John ;
McCarthy, Noel ;
Brander, Christian ;
Learn, Gerald H. ;
Nickle, David ;
Rousseau, Christine ;
Coovadia, Hoosen ;
Mullins, James I. ;
Heckerman, David ;
Walker, Bruce D. ;
Goulder, Philip .
NATURE MEDICINE, 2007, 13 (01) :46-53
[32]   Timing the ancestor of the HIV-1 pandemic strains [J].
Korber, B ;
Muldoon, M ;
Theiler, J ;
Gao, F ;
Gupta, R ;
Lapedes, A ;
Hahn, BH ;
Wolinsky, S ;
Bhattacharya, T .
SCIENCE, 2000, 288 (5472) :1789-1796
[33]   Proliferation, But Not Interleukin 2 Production, of Gag-Specific CD8+ T Cells Is Associated With Low HIV Viremia and High CD4 Counts in HIV-1-infected Chinese Individuals [J].
Li, Haiying ;
Chen, Xinyue ;
Jin, Xia ;
Liu, Zhiying ;
Huang, Xiaojie ;
Cao, Zhenhuan ;
Guo, Caiping ;
Dong, Tao ;
Wu, Hao .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2009, 52 (01) :1-8
[34]   Visualizing Antigen-Specific and Infected Cells in Situ Predicts Outcomes in Early Viral Infection [J].
Li, Qingsheng ;
Skinner, Pamela J. ;
Ha, Sang-Jun ;
Duan, Lijie ;
Mattila, Teresa L. ;
Hage, Aaron ;
White, Cara ;
Barber, Daniel L. ;
O'Mara, Leigh ;
Southern, Peter J. ;
Reilly, Cavan S. ;
Carlis, John V. ;
Miller, Christopher J. ;
Ahmed, Rafi ;
Haase, Ashley T. .
SCIENCE, 2009, 323 (5922) :1726-1729
[35]   Association of polymorphisms in human leukocyte antigen class I and transporter associated with antigen processing genes with resistance to human immunodeficiency virus type 1 infection [J].
Liu, CL ;
Carrington, M ;
Kaslow, RA ;
Gao, XJ ;
Rinaldo, CR ;
Jacobson, LP ;
Margolick, JB ;
Phair, J ;
O'Brien, SJ ;
Detels, R .
JOURNAL OF INFECTIOUS DISEASES, 2003, 187 (09) :1404-1410
[36]   Waiting times for the appearance of cytotoxic T-lymphocyte escape mutants in chronic HIV-1 infection [J].
Liu, Y ;
Mullins, JI ;
Mittler, JE .
VIROLOGY, 2006, 347 (01) :140-146
[37]   Hierarchical targeting of subtype C human immunodeficiency virus type 1 proteins by CD8+ T cells:: Correlation with viral load [J].
Masemola, A ;
Mashishi, T ;
Khoury, G ;
Mohube, P ;
Mokgotho, P ;
Vardas, E ;
Colvin, M ;
Zijenah, L ;
Katzenstein, D ;
Musonda, R ;
Allen, S ;
Kumwenda, N ;
Taha, T ;
Gray, G ;
McIntyre, J ;
Karim, SA ;
Sheppard, HW ;
Gray, CM .
JOURNAL OF VIROLOGY, 2004, 78 (07) :3233-3243
[38]  
Moulton V, 2009, PHYLOGENETIC HANDBOOK: A PRACTICAL APPROACH TO PHYLOGENETIC ANALYSIS AND HYPOTHESIS TESTING, 2ND EDITION, P631
[39]   Viral evolution and escape during primary human immunodeficiency virus-1 infection: implications for vaccine design [J].
Mullins, James I. ;
Rolland, Morgane ;
Allen, Todd M. .
CURRENT OPINION IN HIV AND AIDS, 2008, 3 (01) :60-66
[40]  
Ndongala ML., 2009, Clin Immunol