Polymorphism characteristics of HIV-1 gp120 and 5 hypervariable regions

To investigate polymorphism characteristics of HIV-1 gp120 and its 5 hypervariable regions. Materials and methods: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. Results: We found that the majority of HIV-1 gp120s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. Conclusion: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development.

Polymorphism characteristics of HIV-1 gp120 and 5 hypervariable regions

To investigate polymorphism characteristics of HIV-1 gp120 and its 5 hypervariable regions. Materials and methods: Length polymorphism, potential number of N-linked glycosylation sites (PNGSs), and sequence characteristics of nearly all available global gp120 and its 5 hypervariable regions from HIV-1 subtypes A, B, C, D, G, and H were analyzed. Results: We found that the majority of HIV-1 gp120s have 496-515 amino acids and 21-30 PNGSs, suggesting that a gp120 with this length might be a good virus candidate for vaccine development. Among 5 hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and less PNGSs, while V1 and V4 regions had high levels of length polymorphism and heterogeneity and more PNGSs. These results suggest that reducing the polymorphism, heterogeneity, and PNGSs of the 4 hypervariable regions should be taken into account in AIDS vaccine development for effectively eliciting immune response. Except for subtype D, other subtypes have the consensus V3 sequences with R5 tropism, implying that the majority of HIV-1 strains are R5 strains. Conclusion: The results suggest that CCR5 antagonists may be extremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development.

___

  • Plantier JC, Leoz M, Dickerson JE, De Oliveira F, Cordonnier F, Lemee V, Damond F, Robertson DL, Simon F. A new human immunodeficiency virus derived from gorillas. Nat Med 2009; 15: 871–872. 2.
  • Keele BF, Van Heuverswyn F, Li Y, Bailes E, Takehisa J, Santiago
  • ML, Bibollet-Ruche F, Chen Y, Wain LV, Liegeois F et al.
  • Chimpanzee reservoirs of pandemic and nonpandemic HIV-1.
  • Science 2006; 313: 523–526.
  • Gray ES, Taylor N, Wycuff D, Moore PL, Tomaras GD, Wibmer CK, Puren A, DeCamp A, Gilbert PB, Wood B et al. Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors. J Virol 2009; 83: 8925–8937.
  • Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, Pietzsch J, Ott RG, Anthony RM, Zebroski H, Hurley A et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 2009; 458: 636–640.
  • Willey RL, Rutledge RA, Dias S, Folks T, Theodore T, Buckler CE, Martin MA. Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus. Proc Natl Acad Sci U S A 1986; 83: 5038–5042.
  • Hwang SS, Boyle TJ, Lyerly HK, Cullen BR. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science 1991; 253: 71–74.
  • Chesebro B, Wehrly K, Nishio J, Perryman S. Macrophage- tropic human immunodeficiency virus isolates from different patients exhibit unusual V3 envelope sequence homogeneity in comparison with T-cell-tropic isolates: definition of critical amino acids involved in cell tropism. J Virol 1992; 66: 6547– 6554.
  • Shioda T, Levy JA, Cheng-Mayer C. Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell- line and macrophage tropism of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 1992; 89: 9434–9438.
  • Ghaffari G, Tuttle DL, Briggs D, Burkhardt BR, Bhatt D, Andiman WA, Sleasman JW, Goodenow MM. Complex determinants in human immunodeficiency virus type 1 envelope gp120 mediate CXCR4-dependent infection of macrophages. J Virol 2005; 79: 13250–13261.
  • Smyth RJ, Yi Y, Singh A, Collman RG. Determinants of entry cofactor utilization and tropism in a dualtropic human immunodeficiency virus type 1 primary isolate. J Virol 1998; 72: 4478–4484.
  • Sullivan N, Thali M, Furman C, Ho DD, Sodroski J. Effect of amino acid changes in the V1/V2 region of the human immunodeficiency virus type 1 gp120 glycoprotein on subunit association, syncytium formation, and recognition by a neutralizing antibody. J Virol 1993; 67: 3674–3679.
  • Jurkiewicz E, Hunsmann G, Schaffner J, Nisslein T, Luke W, Petry H. Identification of the V1 region as a linear neutralizing epitope of the simian immunodeficiency virus SIVmac envelope glycoprotein. J Virol 1997; 71: 9475–9481.
  • Pinter A, Honnen WJ, He Y, Gorny MK, Zolla-Pazner S, Kayman SC. The V1/V2 domain of gp120 is a global regulator of the sensitivity of primary human immunodeficiency virus type 1 isolates to neutralization by antibodies commonly induced upon infection. J Virol 2004; 78: 5205–5215.
  • Riddle TM, Shire NJ, Sherman MS, Franco KF, Sheppard HW, Nelson JA. Sequential turnover of human immunodeficiency virus type 1 env throughout the course of infection. J Virol 2006; 80: 10591–10599.
  • Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998; 393: 648–659.
  • Curlin ME, Zioni R, Hawes SE, Liu Y, Deng W, Gottlieb GS, Zhu T, Mullins JI. HIV-1 envelope subregion length variation during disease progression. PLoS Pathog 2010; 6: e1001228.
  • Crooks GE, Hon G, Chandonia JM, Brenner SE. WebLogo: a sequence logo generator. Genome Res 2004; 14: 1188–1190.
  • Xu S, Huang X, Xu H, Zhang C. Improved prediction of coreceptor usage and phenotype of HIV-1 based on combined features of V3 loop sequence using random forest. J Microbiol 2007; 45: 441–446.
  • Zhang C, Xu S, Wei J, Guo H. Predicted co-receptor tropism and sequence characteristics of China HIV-1 V3 loops: implications for the future usage of CCR5 antagonists and AIDS vaccine development. Int J Infect Dis 2009; 13: e212–216.
  • Regoes RR, Bonhoeffer S. The HIV coreceptor switch: a population dynamical perspective. Trends Microbiol 2005; 13: 269–277.
  • Salemi M, Burkhardt BR, Gray RR, Ghaffari G, Sleasman JW, Goodenow MM. Phylodynamics of HIV-1 in lymphoid and non-lymphoid tissues reveals a central role for the thymus in emergence of CXCR4-using quasispecies. PLoS One 2007; 2: e950.
  • Barroso H, Borrego P, Bartolo I, Marcelino JM, Familia C, Quintas A, Taveira N. Evolutionary and structural features of the C2, V3 and C3 envelope regions underlying the differences in HIV-1 and HIV-2 biology and infection. PLoS One 2011; 6: e14548.
  • Mosier D, Sieburg H. Macrophage-tropic HIV: critical for AIDS pathogenesis? Immunol Today 1994; 15: 332–339.
  • Zhu T, Mo H, Wang N, Nam DS, Cao Y, Koup RA, Ho DD. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 1993; 261: 1179–1181.
  • Philpott SM. HIV-1 coreceptor usage, transmission, and disease progression. Curr HIV Res 2003; 1: 217–227.
  • Poveda E, Briz V, Quinones-Mateu M, Soriano V. HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors. AIDS 2006; 20: 1359–1367.
  • Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 1999; 17: 657–700.
  • Bunnik EM, Quakkelaar ED, van Nuenen AC, Boeser-Nunnink B, Schuitemaker H. Increased neutralization sensitivity of recently emerged CXCR4-using human immunodeficiency virus type 1 strains compared to coexisting CCR5-using variants from the same patient. J Virol 2007; 81: 525–531.
  • Parren PW, Moore JP, Burton DR, Sattentau QJ. The neutralizing antibody response to HIV-1: viral evasion and escape from humoral immunity. AIDS 1999; 13 (Suppl. A): S137–S162.
  • Zhang C, Ding N, Chen K, Yang R. Complex positive selection pressures drive the evolution of HIV-1 with different co- receptor tropisms. Sci China Life Sci 2010; 53: 1204–1214.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Structural chromosomal abnormalities in couples with recurrent abortion in Egypt

Nagwa E.a. GABOON, Ahmed Ramy MOHAMED, Solaf M. ELSAYED, Osama K. ZAKI, Mohamed A. ELSAYED

Evaluation of autoinflammatory disease genes in nasal polyposis*

Mehmet Ali ÇETİN, Hacı Hüseyin DERE, Sibel ÖZDAŞ, Sabri KÖSEOĞLU, Serdar ENSARİ, Aykut İKİNCİOĞULLARI, Kürşat Murat ÖZCAN, Talih ÖZDAŞ

Analysis of vacA/cagA genotypes/status in Helicobacter pylori isolates from Iranian children and their association with clinical outcome

Tahereh FALSAFI, Afsaneh KHANI, Fatemeh MAHJOUB, Ezat ASGARANI, Nazli SOTOUDEH

The effect of total intravenous anesthesia on the postoperative cognitive functions of young and elderly patients after lumbar disk surgery

Gizem İLVAN, Hatice Zerrin ÖZKÖSE

Protective effects of erdosteine, vitamin E, and vitamin C on renal injury induced by the ischemia-reperfusion of the hind limbs in rats

Rana SIRMALI, Abdullah ARMAĞAN, Faruk ÖKTEM, Efkan UZ, Aynur KIRBAŞ, Soner DÖNMEZ, Hacı Ramazan YILMAZ, Mesrur Selçuk SILAY, Mehmet SIRMALI

Effects on quinolone resistance due to the biofilm formation activity in Ureaplasma urealyticum

Chunyan FENG, Ya HUANG, Yunsong YU, Guorong DUAN, Yuying DAI, Ke DONG, Qingtian LI

Assessment of nasal mucociliary clearance in anesthetists

Eyüp HORASANLI, Aydın ACAR, Bünyamin MUSLU, Melih ÇAYÖNÜ, Murat ÇİMENCAN, Serkan KAYABAŞI

Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer

Muhammet ÇALIK, Elif DEMİRCİ, Eren ALTUN, İlknur ÇALIK

Utility of M30, an apoptotic serum marker, in liver diseases

Akif ALTINBAŞ, Şahin ÇOBAN, Ömer BAŞAR, Osman YÜKSEL

An alternative marker of low-density lipoprotein cholesterol in coronary artery disease: non-high-density lipoprotein cholesterol

Müjgan ERCAN, Esra OĞUZ, Fatma Meriç YILMAZ, Nihal BOĞDAYCIOĞLU, Kübranur ÜNAL, Deniz ŞAHİN, Sema UYSAL