The genetic basis of resistance to HIV infection and disease progression

Susceptibility to HIV infection and the modulation of disease progression are strictly dependent on inter-individual variability, much of which is secondary to host genetic heterogeneity. The study of host factors that control these phenomena relies not only on candidate gene approaches but also on unbiased genome-wide genetic and functional analyses. Additional new insights stem from the study of mechanisms that control the expression of host and viral genes, such as miRNA. The genetic host factors that have been suggested to be associated either with resistance to HIV-1 infection or with absent/delayed progression to AIDS are nevertheless unable to fully justify the phenomenon of differential susceptibility to HIV. Multidisciplinary approaches are needed to further analyze individuals who deviate from the expected response to HIV exposure/infection. Results of these analyses will facilitate the identification of novel targets that could be exploited in the setting up of innovative therapeutic or vaccine approaches.

[1]  K. Shianna,et al.  Host genetics of HIV acquisition and viral control. , 2013, Annual review of medicine.

[2]  T. Naoe,et al.  Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency , 2012, AIDS Research and Therapy.

[3]  Kuan-Teh Jeang,et al.  MicroRNAs and HIV-1: Complex Interactions* , 2012, The Journal of Biological Chemistry.

[4]  Kuan-Teh Jeang,et al.  The extent of sequence complementarity correlates with the potency of cellular miRNA-mediated restriction of HIV-1 , 2012, Nucleic acids research.

[5]  C. Wachihi,et al.  A Genetic Polymorphism of FREM1 Is Associated with Resistance against HIV Infection in the Pumwani Sex Worker Cohort , 2012, Journal of Virology.

[6]  Ren-Rong Tian,et al.  Translation of Pur‐α is targeted by cellular miRNAs to modulate the differentiation‐dependent susceptibility of monocytes to HIV‐1 infection , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  L. Lopalco,et al.  Stable changes in CD4+ T lymphocyte miRNA expression after exposure to HIV-1. , 2012, Blood.

[8]  Hong-Sheng Zhang,et al.  MiR-217 is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation by down-regulation of SIRT1. , 2012, Biochimica et biophysica acta.

[9]  A. Telenti,et al.  Host genes important to HIV replication and evolution. , 2012, Cold Spring Harbor perspectives in medicine.

[10]  O. Delaneau,et al.  Multicohort genomewide association study reveals a new signal of protection against HIV-1 acquisition. , 2012, The Journal of infectious diseases.

[11]  E. Campbell,et al.  The Cell Biology of TRIM5α , 2012, Current HIV/AIDS Reports.

[12]  A. Hill,et al.  Human genetic susceptibility to infectious disease , 2012, Nature Reviews Genetics.

[13]  G. Boucher,et al.  Microarray Analysis of HIV Resistant Female Sex Workers Reveal a Gene Expression Signature Pattern Reminiscent of a Lowered Immune Activation State , 2012, PloS one.

[14]  M. Clerici,et al.  A Common Polymorphism in TLR3 Confers Natural Resistance to HIV-1 Infection , 2012, The Journal of Immunology.

[15]  J. Clements,et al.  Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients , 2012, Retrovirology.

[16]  Andrew P. Rice,et al.  Regulation of Cyclin T1 and HIV-1 Replication by MicroRNAs in Resting CD4+ T Lymphocytes , 2011, Journal of Virology.

[17]  K. Shianna,et al.  Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure , 2011, PloS one.

[18]  J. Neefjes,et al.  Towards a systems understanding of MHC class I and MHC class II antigen presentation , 2011, Nature Reviews Immunology.

[19]  N. Bresolin,et al.  A POSITIVELY SELECTED APOBEC3H HAPLOTYPE IS ASSOCIATED WITH NATURAL RESISTANCE TO HIV‐1 INFECTION , 2011, Evolution; international journal of organic evolution.

[20]  Guihua Sun,et al.  MicroRNAs and their potential involvement in HIV infection. , 2011, Trends in pharmacological sciences.

[21]  K. Shianna,et al.  Copy Number Variation of KIR Genes Influences HIV-1 Control , 2011, PLoS biology.

[22]  M. Nair,et al.  MicroRNA: implications in HIV, a brief overview , 2011, Journal of NeuroVirology.

[23]  O. Delaneau,et al.  Genome-Wide Association Scan in HIV-1-Infected Individuals Identifying Variants Influencing Disease Course , 2011, PloS one.

[24]  J. Turpin,et al.  Outcomes of a National Institute of Allergy and Infectious Diseases Workshop on understanding HIV-exposed but seronegative individuals. , 2011, AIDS research and human retroviruses.

[25]  S. Khakoo,et al.  KIR/HLA Interactions and Pathogen Immunity , 2011, Journal of biomedicine & biotechnology.

[26]  R. Maserati,et al.  Under representation of the inhibitory KIR3DL1 molecule and the KIR3DL1+/BW4+ complex in HIV exposed seronegative individuals. , 2011, The Journal of infectious diseases.

[27]  Jacques Fellay,et al.  Genome-Wide Association Study Identifies Single Nucleotide Polymorphism in DYRK1A Associated with Replication of HIV-1 in Monocyte-Derived Macrophages , 2011, PloS one.

[28]  K. Shianna,et al.  Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population , 2011, AIDS.

[29]  Jack T Stapleton,et al.  The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation , 2010, Science.

[30]  N. Bresolin,et al.  Genetic diversity at endoplasmic reticulum aminopeptidases is maintained by balancing selection and is associated with natural resistance to HIV-1 infection. , 2010, Human molecular genetics.

[31]  C. Wachihi,et al.  HIV‐exposed seronegative commercial sex workers show a quiescent phenotype in the CD4+ T cell compartment and reduced expression of HIV‐dependent host factors. , 2010, The Journal of infectious diseases.

[32]  Warren W. Kretzschmar,et al.  Balancing Selection Maintains a Form of ERAP2 that Undergoes Nonsense-Mediated Decay and Affects Antigen Presentation , 2010, PLoS genetics.

[33]  O. Delaneau,et al.  Multiple-cohort genetic association study reveals CXCR6 as a new chemokine receptor involved in long-term nonprogression to AIDS. , 2010, The Journal of infectious diseases.

[34]  K. Shianna,et al.  Host determinants of HIV-1 control in African Americans. , 2010, The Journal of infectious diseases.

[35]  C. Winkler,et al.  Host genes associated with HIV/AIDS: advances in gene discovery. , 2010, Trends in genetics : TIG.

[36]  M. Clerici,et al.  TLR Activation Pathways in HIV-1–Exposed Seronegative Individuals , 2010, The Journal of Immunology.

[37]  T. Ndung’u,et al.  APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load , 2010, AIDS.

[38]  J. Goedert,et al.  HLA-B*35-Px–mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses , 2009, The Journal of experimental medicine.

[39]  E. Thiel,et al.  Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. , 2009, The New England journal of medicine.

[40]  P. Hunt Natural control of HIV-1 replication and long-term nonprogression: overlapping but distinct phenotypes. , 2009, The Journal of infectious diseases.

[41]  J. Blankson,et al.  Elucidating the elite: mechanisms of control in HIV-1 infection. , 2009, Trends in pharmacological sciences.

[42]  Elizabeth T. Cirulli,et al.  Common Genetic Variation and the Control of HIV-1 in Humans , 2009, PLoS genetics.

[43]  B. Agan,et al.  Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study. , 2009, The Journal of infectious diseases.

[44]  J. Phair,et al.  CCL3L1 and HIV/AIDS susceptibility , 2009, Nature Medicine.

[45]  D. Clayton,et al.  Experimental aspects of copy number variant assays at CCL3L1 , 2009, Nature Medicine.

[46]  T. Nakajima,et al.  Impact of novel TRIM5α variants, Gly110Arg and G176del, on the anti-HIV-1 activity and the susceptibility to HIV-1 infection , 2009, AIDS.

[47]  Hong Cao,et al.  Cellular microRNA and P bodies modulate host-HIV-1 interactions. , 2009, Molecular cell.

[48]  David Burgner,et al.  HLA and Infectious Diseases , 2009, Clinical Microbiology Reviews.

[49]  S. Ross Are Viruses Inhibited by APOBEC3 Molecules from Their Host Species? , 2009, PLoS pathogens.

[50]  G. Reyes-Terán,et al.  APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression , 2009, Retrovirology.

[51]  D. Metzger,et al.  Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. , 2009, Blood.

[52]  R. Detels The 'immunologic advantage' of HIV-exposed seronegative individuals , 2009 .

[53]  B. Walker,et al.  Elite control of HIV infection: implications for vaccine design , 2009, Expert opinion on biological therapy.

[54]  M. Clerici,et al.  Genetic correlates of protection against HIV infection: the ally within , 2009, Journal of internal medicine.

[55]  A. Rice,et al.  miR-198 Inhibits HIV-1 Gene Expression and Replication in Monocytes and Its Mechanism of Action Appears To Involve Repression of Cyclin T1 , 2009, PLoS pathogens.

[56]  M. Essex,et al.  Reduced Viral Replication Capacity of Human Immunodeficiency Virus Type 1 Subtype C Caused by Cytotoxic-T-Lymphocyte Escape Mutations in HLA-B57 Epitopes of Capsid Protein , 2008, Journal of Virology.

[57]  V. Scaria,et al.  Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication , 2008, Retrovirology.

[58]  M. Carrington,et al.  KIR-HLA intercourse in HIV disease. , 2008, Trends in microbiology.

[59]  P. Sharp,et al.  Small RNA Regulators of Gene Expression , 2008, Cell.

[60]  Philip J. R. Goulder,et al.  Impact of MHC class I diversity on immune control of immunodeficiency virus replication , 2008, Nature Reviews Immunology.

[61]  Ma Luo,et al.  Human Immunodeficiency Virus (HIV) Type 1 Proviral Hypermutation Correlates with CD4 Count in HIV-Infected Women from Kenya , 2008, Journal of Virology.

[62]  N. Nagelkerke,et al.  Associations of human leukocyte antigen DRB with resistance or susceptibility to HIV-1 infection in the Pumwani Sex Worker Cohort , 2008, AIDS.

[63]  M. Carrington,et al.  Maternal HLA homozygosity and mother-child HLA concordance increase the risk of vertical transmission of HIV-1. , 2008, The Journal of infectious diseases.

[64]  N. Nagelkerke,et al.  Human leukocyte antigen-DQ alleles and haplotypes and their associations with resistance and susceptibility to HIV-1 infection , 2008, AIDS.

[65]  J. Routy,et al.  Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected individuals , 2008, AIDS.

[66]  Terri Wrin,et al.  Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. , 2008, The Journal of infectious diseases.

[67]  H. Schuitemaker,et al.  The Effect of Trim5 Polymorphisms on the Clinical Course of HIV-1 Infection , 2008, PLoS pathogens.

[68]  Jialing Huang,et al.  Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes , 2007, Nature Medicine.

[69]  Todd M. Allen,et al.  Escape from the Dominant HLA-B27-Restricted Cytotoxic T-Lymphocyte Response in Gag Is Associated with a Dramatic Reduction in Human Immunodeficiency Virus Type 1 Replication , 2007, Journal of Virology.

[70]  Jacques Fellay,et al.  A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1 , 2007, Science.

[71]  L. Lopalco,et al.  Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G: a possible role in the resistance to HIV of HIV-exposed seronegative individuals. , 2007, The Journal of infectious diseases.

[72]  Hulin Wu,et al.  APOBEC3G levels predict rates of progression to AIDS , 2007, Retrovirology.

[73]  Pascal Barbry,et al.  Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication , 2007, Science.

[74]  S. S. Chauhan,et al.  Distribution of CCR5delta32, CCR2-64I and SDF1-3'A and plasma levels of SDF-1 in HIV-1 seronegative North Indians. , 2007, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[75]  L. Elviri,et al.  Postgenomic up-regulation of CCL3L1 expression in HTLV-2-infected persons curtails HIV-1 replication. , 2007, Blood.

[76]  B. Vuylsteke,et al.  Cutting Edge: Resistance to HIV-1 Infection among African Female Sex Workers Is Associated with Inhibitory KIR in the Absence of Their HLA Ligands1 , 2006, The Journal of Immunology.

[77]  Roger Detels,et al.  Effects of human TRIM5α polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection , 2006 .

[78]  M. Alary,et al.  APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians , 2006, AIDS.

[79]  Christos J. Petropoulos,et al.  Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus , 2006, The Journal of experimental medicine.

[80]  John Bui,et al.  Genetic Association of the Antiviral Restriction Factor TRIM5α with Human Immunodeficiency Virus Type 1 Infection , 2006, Journal of Virology.

[81]  S. Rowland-Jones,et al.  Identification of a novel HLA B*57 restricted cytotoxic T-lymphocyte epitope within HIV-1 rev , 2006, AIDS.

[82]  Vinod Scaria,et al.  Targets for human encoded microRNAs in HIV genes. , 2005, Biochemical and biophysical research communications.

[83]  S. Hunt,et al.  Genome-Wide Associations of Gene Expression Variation in Humans , 2005, PLoS genetics.

[84]  L. Meyer,et al.  Spontaneous control of viral load and CD4 cell count progression among HIV-1 seroconverters , 2005, AIDS.

[85]  Mario Clerici,et al.  Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians , 2005, AIDS.

[86]  B. Rovin,et al.  The Influence of CCL 3 L 1 Gene – Containing Segmental Duplications on HIV-1 / AIDS Susceptibility , 2009 .

[87]  V. Kim,et al.  The Drosha-DGCR8 complex in primary microRNA processing. , 2004, Genes & development.

[88]  Amalio Telenti,et al.  APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS , 2004, Journal of Virology.

[89]  Stephen J O'Brien,et al.  Human genes that limit AIDS , 2004, Nature Genetics.

[90]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[91]  Todd M. Allen,et al.  Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection , 2003, AIDS.

[92]  Stephen J O'Brien,et al.  The influence of HLA genotype on AIDS. , 2003, Annual review of medicine.

[93]  N. Saksena,et al.  Mechanisms involved in non-progressive HIV disease. , 2003, AIDS reviews.

[94]  T. Hodge,et al.  Polymorphisms in the CCR5 coding and noncoding regions among HIV type 1-exposed, persistently seronegative female sex-workers from Thailand. , 2003, AIDS research and human retroviruses.

[95]  M. Lejeune,et al.  Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A genotype, and expression of CXCR4 on T lymphocytes: their impact on resistance to human immunodeficiency virus type 1 infection and its progression. , 2002, The Journal of infectious diseases.

[96]  Tao Dong,et al.  Cross-reactive cytotoxic T lymphocytes against a HIV-1 p24 epitope in slow progressors with B*57 , 2002, AIDS.

[97]  Y. Takebe,et al.  Genetic analysis of HIV-1 discordant couples in Thailand: association of CCR2 64I homozygosity with HIV-1-negative status. , 2002, Journal of acquired immune deficiency syndromes.

[98]  J J Goedert,et al.  Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. , 2001, The New England journal of medicine.

[99]  Edward C. Holmes,et al.  Clustered Mutations in HIV-1 Gag Are Consistently Required for Escape from Hla-B27–Restricted Cytotoxic T Lymphocyte Responses , 2001, The Journal of experimental medicine.

[100]  S. Rowland-Jones,et al.  Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. , 2000, The Journal of infectious diseases.

[101]  F. Marincola,et al.  HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[102]  J. Goedert,et al.  HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. , 1999, Science.

[103]  S. H. van der Burg,et al.  Characterization of HLA-B57-restricted human immunodeficiency virus type 1 Gag- and RT-specific cytotoxic T lymphocyte responses. , 1998, The Journal of general virology.

[104]  J. Mills,et al.  HIV‐1 DNA and mRNA concentrations are similar in peripheral blood monocytes and alveolar macrophages in HIV‐1‐infected individuals , 1998, AIDS.

[105]  N. Nagelkerke,et al.  Mother-child class I HLA concordance increases perinatal human immunodeficiency virus type 1 transmission. , 1998, The Journal of infectious diseases.

[106]  C. Mackay,et al.  Interaction of Chemokine Receptor CCR5 with its Ligands: Multiple Domains for HIV-1 gp120 Binding and a Single Domain for Chemokine Binding , 1997, The Journal of experimental medicine.

[107]  Martin A. Nowak,et al.  Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS , 1997, Nature Medicine.

[108]  R. Phillips,et al.  Novel, cross-restricted, conserved, and immunodominant cytotoxic T lymphocyte epitopes in slow progressors in HIV type 1 infection. , 1996, AIDS research and human retroviruses.

[109]  N. Nagelkerke,et al.  Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya , 1996, The Lancet.

[110]  Marc Parmentier,et al.  Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene , 1996, Nature.

[111]  Stephen C. Peiper,et al.  Identification of a major co-receptor for primary isolates of HIV-1 , 1996, Nature.

[112]  J. Berzofsky,et al.  Cell-mediated immune response to human immunodeficiency virus (HIV) type 1 in seronegative homosexual men with recent sexual exposure to HIV-1. , 1992, The Journal of infectious diseases.

[113]  Steven M. Wolinsky,et al.  Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. , 1989, The New England journal of medicine.

[114]  N. Nagelkerke,et al.  Heterogeneity in susceptibility to HIV-1 in continuously exposed prostitutes. , 1992 .

[115]  A. Fauci,et al.  The immunopathogenesis of HIV infection. , 1989, Advances in immunology.