4 †Present address: Laboratory of Experimental Virology, Center of Infection and Immunity Amsterdam (CINIMA), Academical Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Human immunodeficiency virus type 1 (HIV-1) is classified into different phylogenetic subtypes, with subtype C representing more than half of the novel infections globally. However, there are relatively few subtype C envelopes available for study. We amplified 18 unique env genes from 13 patients who were infected with subtype C HIV-1 in six African countries and in Scotland to create replication-competent viruses. These envelopes are phylogenetically diverse across the subtype C spectrum, and have on average more N-linked glycosylation sites and slightly longer variable loops than previously described C envelopes. We found that CCR3 coreceptor usage is less prevalent in subtype C than in subtype B viruses, and these envelopes have varied sensitivity to neutralization. The subtype C chimeric viruses generated in this study will be useful for evaluating the breadth of neutralizing antibodies and other entry inhibitors.
Aasa-Chapman, M. M., Aubin, K., Williams, I. & McKnight, A.(2006a). Primary CCR5 only using HIV-1 isolates does not accurately represent the in vivo replicating quasi-species. Virology351, 489–496.[CrossRef][Google Scholar]
Aasa-Chapman, M. M., Seymour, C. R., Williams, I. & McKnight, A.(2006b). Novel envelope determinants for CCR3 use by human immunodeficiency virus. J Virol80, 10884–10889.[CrossRef][Google Scholar]
Abebe, A., Demissie, D., Goudsmit, J., Brouwer, M., Kuiken, C. L., Pollakis, G., Schuitemaker, H., Fontanet, A. L. & Rinke de Wit, T. F.(1999). HIV-1 subtype C syncytium- and non-syncytium-inducing phenotypes and coreceptor usage among Ethiopian patients with AIDS. AIDS13, 1305–1311.[CrossRef][Google Scholar]
Agrawal, L., Maxwell, C. R., Peters, P. J., Clapham, P. R., Liu, S. M., Mackay, C. R. & Strayer, D. S.(2009). Complexity in human immunodeficiency virus type 1 (HIV-1) co-receptor usage: roles of CCR3 and CCR5 in HIV-1 infection of monocyte-derived macrophages and brain microglia. J Gen Virol90, 710–722.[CrossRef][Google Scholar]
Binley, J. M., Wrin, T., Korber, B., Zwick, M. B., Wang, M., Chappey, C., Stiegler, G., Kunert, R., Zolla-Pazner, S. & other authors(2004). Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol78, 13232–13252.[CrossRef][Google Scholar]
Bjorndal, A., Sonnerborg, A., Tscherning, C., Albert, J. & Fenyo, E. M.(1999). Phenotypic characteristics of human immunodeficiency virus type 1 subtype C isolates of Ethiopian AIDS patients. AIDS Res Hum Retroviruses15, 647–653.[CrossRef][Google Scholar]
Brown, B. K., Darden, J. M., Tovanabutra, S., Oblander, T., Frost, J., Sanders-Buell, E., de Souza, M. S., Birx, D. L., McCutchan, F. E. & Polonis, V. R.(2005). Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG, for the development and assessment of candidate vaccines. J Virol79, 6089–6101.[CrossRef][Google Scholar]
Bures, R., Morris, L., Williamson, C., Ramjee, G., Deers, M., Fiscus, S. A., Abdool-Karim, S. & Montefiori, D. C.(2002). Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa. J Virol76, 2233–2244.[CrossRef][Google Scholar]
Calarese, D. A., Scanlan, C. N., Zwick, M. B., Deechongkit, S., Mimura, Y., Kunert, R., Zhu, P., Wormald, M. R., Stanfield, R. L. & other authors(2003). Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science300, 2065–2071.[CrossRef][Google Scholar]
Cardoso, R. M., Zwick, M. B., Stanfield, R. L., Kunert, R., Binley, J. M., Katinger, H., Burton, D. R. & Wilson, I. A.(2005). Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41. Immunity22, 163–173.[CrossRef][Google Scholar]
Cardozo, T., Kimura, T., Philpott, S., Weiser, B., Burger, H. & Zolla-Pazner, S.(2007). Structural basis for coreceptor selectivity by the HIV type 1 V3 loop. AIDS Res Hum Retroviruses23, 415–426.[CrossRef][Google Scholar]
Cecilia, D., Kulkarni, S. S., Tripathy, S. P., Gangakhedkar, R. R., Paranjape, R. S. & Gadkari, D. A.(2000). Absence of coreceptor switch with disease progression in human immunodeficiency virus infections in India. Virology271, 253–258.[CrossRef][Google Scholar]
Choe, H., Farzan, M., Sun, Y., Sullivan, N., Rollins, B., Ponath, P. D., Wu, L., Mackay, C. R., LaRosa, G. & other authors(1996). The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell85, 1135–1148.[CrossRef][Google Scholar]
Cilliers, T., Nhlapo, J., Coetzer, M., Orlovic, D., Ketas, T., Olson, W. C., Moore, J. P., Trkola, A. & Morris, L.(2003). The CCR5 and CXCR4 coreceptors are both used by human immunodeficiency virus type 1 primary isolates from subtype C. J Virol77, 4449–4456.[CrossRef][Google Scholar]
Deng, H., Liu, R., Ellmeier, W., Choe, S., Unutmaz, D., Burkhart, M., Di Marzio, P., Marmon, S., Sutton, R. E. & other authors(1996). Identification of a major co-receptor for primary isolates of HIV-1. Nature381, 661–666.[CrossRef][Google Scholar]
Fernandez-Garcia, A., Cuevas, M. T., Munoz-Nieto, M., Ocampo, A., Pinilla, M., Garcia, V., Serrano-Bengoechea, E., Lezaun, M. J., Delgado, E. & other authors(2009). Development of a panel of well-characterized human immunodeficiency virus type 1 isolates from newly diagnosed patients including acute and recent infections. AIDS Res Hum Retroviruses25, 93–102.[CrossRef][Google Scholar]
Forsman, A., Beirnaert, E., Aasa-Chapman, M. M., Hoorelbeke, B., Hijazi, K., Koh, W., Tack, V., Szynol, A., Kelly, C. & other authors(2008). Llama antibody fragments with cross-subtype human immunodeficiency virus type 1 (HIV-1)-neutralizing properties and high affinity for HIV-1 gp120. J Virol82, 12069–12081.[CrossRef][Google Scholar]
Gray, E. S., Meyers, T., Gray, G., Montefiori, D. C. & Morris, L.(2006). Insensitivity of paediatric HIV-1 subtype C viruses to broadly neutralising monoclonal antibodies raised against subtype B. PLoS Med3, e255[CrossRef][Google Scholar]
Hoffman, T. L., Stephens, E. B., Narayan, O. & Doms, R. W.(1998). HIV type I envelope determinants for use of the CCR2b, CCR3, STRL33, and APJ coreceptors. Proc Natl Acad Sci U S A95, 11360–11365.[CrossRef][Google Scholar]
Isaacman-Beck, J., Hermann, E. A., Yi, Y., Ratcliffe, S. J., Mulenga, J., Allen, S., Hunter, E., Derdeyn, C. A. & Collman, R. G.(2009). Heterosexual transmission of human immunodeficiency virus type 1 subtype C: macrophage tropism, alternative coreceptor use, and the molecular anatomy of CCR5 utilization. J Virol83, 8208–8220.[CrossRef][Google Scholar]
Koh, W. W., Steffensen, S., Gonzalez, M., Hoorelbeke, B., Gorlani, A., Szynol, A., Forsman, A., Aasa-Chapman, M. M., de Haard, H. & other authors(2010). Generation of a family-specific phage library of llama single chain antibody fragments that neutralize HIV-1. J Biol Chem285, 19116–19124.[CrossRef][Google Scholar]
Li, M., Gao, F., Mascola, J. R., Stamatatos, L., Polonis, V. R., Koutsoukos, M., Voss, G., Goepfert, P., Gilbert, P. & other authors(2005). Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol79, 10108–10125.[CrossRef][Google Scholar]
Li, B., Decker, J. M., Johnson, R. W., Bibollet-Ruche, F., Wei, X., Mulenga, J., Allen, S., Hunter, E., Hahn, B. H. & other authors(2006a). Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1. J Virol80, 5211–5218.[CrossRef][Google Scholar]
Li, M., Salazar-Gonzalez, J. F., Derdeyn, C. A., Morris, L., Williamson, C., Robinson, J. E., Decker, J. M., Li, Y., Salazar, M. G. & other authors(2006b). Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa. J Virol80, 11776–11790.[CrossRef][Google Scholar]
McKeating, J. A., Zhang, Y. J., Arnold, C., Frederiksson, R., Fenyo, E. M. & Balfe, P.(1996). Chimeric viruses expressing primary envelope glycoproteins of human immunodeficiency virus type I show increased sensitivity to neutralization by human sera. Virology220, 450–460.[CrossRef][Google Scholar]
Montefiori, D. C.(2004). Evaluating neutralizing antibodies against HIV, SIV and SHIV in luciferase reporter gene assays. In Current Protocols in Immunology, pp. 12.11.1–12.11.15. Edited by A. M. K. J. E. Coligan, D. H. Margulies, E. M. Shevach, W. Strober & R. Coico. New York, NY: John Wiley & Sons.
Morris, L., Cilliers, T., Bredell, H., Phoswa, M. & Martin, D. J.(2001). CCR5 is the major coreceptor used by HIV-1 subtype C isolates from patients with active tuberculosis. AIDS Res Hum Retroviruses17, 697–701.[CrossRef][Google Scholar]
Muster, T., Steindl, F., Purtscher, M., Trkola, A., Klima, A., Himmler, G., Ruker, F. & Katinger, H.(1993). A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol67, 6642–6647.
[Google Scholar]
Nedellec, R., Coetzer, M., Shimizu, N., Hoshino, H., Polonis, V. R., Morris, L., Martensson, U. E., Binley, J., Overbaugh, J. & Mosier, D. E.(2009). Virus entry via the alternative coreceptors CCR3 and FPRL1 differs by human immunodeficiency virus type 1 subtype. J Virol83, 8353–8363.[CrossRef][Google Scholar]
Ofek, G., Tang, M., Sambor, A., Katinger, H., Mascola, J. R., Wyatt, R. & Kwong, P. D.(2004). Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J Virol78, 10724–10737.[CrossRef][Google Scholar]
Rao, V. R., Sas, A. R., Eugenin, E. A., Siddappa, N. B., Bimonte-Nelson, H., Berman, J. W., Ranga, U., Tyor, W. R. & Prasad, V. R.(2008). HIV-1 clade-specific differences in the induction of neuropathogenesis. J Neurosci28, 10010–10016.[CrossRef][Google Scholar]
Sanders, R. W., Venturi, M., Schiffner, L., Kalyanaraman, R., Katinger, H., Lloyd, K. O., Kwong, P. D. & Moore, J. P.(2002). The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol76, 7293–7305.[CrossRef][Google Scholar]
Scanlan, C. N., Pantophlet, R., Wormald, M. R., Ollmann Saphire, E., Stanfield, R., Wilson, I. A., Katinger, H., Dwek, R. A., Rudd, P. M. & Burton, D. R.(2002). The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of α1→2 mannose residues on the outer face of gp120. J Virol76, 7306–7321.[CrossRef][Google Scholar]
Soda, Y., Shimizu, N., Jinno, A., Liu, H. Y., Kanbe, K., Kitamura, T. & Hoshino, H.(1999). Establishment of a new system for determination of coreceptor usages of HIV based on the human glioma NP-2 cell line. Biochem Biophys Res Commun258, 313–321.[CrossRef][Google Scholar]
UNAIDS/WHO(2009). AIDS epidemic update: November 2009.
Wu, L., Yang, Z. Y., Xu, L., Welcher, B., Winfrey, S., Shao, Y., Mascola, J. R. & Nabel, G. J.(2006). Cross-clade recognition and neutralization by the V3 region from clade C human immunodeficiency virus-1 envelope. Vaccine24, 4995–5002.[CrossRef][Google Scholar]
Xiao, L., Owen, S. M., Goldman, I., Lal, A. A., deJong, J. J., Goudsmit, J. & Lal, R. B.(1998). CCR5 coreceptor usage of non-syncytium-inducing primary HIV-1 is independent of phylogenetically distinct global HIV-1 isolates: delineation of consensus motif in the V3 domain that predicts CCR-5 usage. Virology240, 83–92.[CrossRef][Google Scholar]
Yirrell, D. L., Shaw, L., Burns, S. M., Cameron, S. O., Quigg, M., Campbell, E. & Goldberg, D.(2004). HIV-1 subtype in Scotland: the establishment of a national surveillance system. Epidemiol Infect132, 693–698.[CrossRef][Google Scholar]
Zhang, H., Hoffmann, F., He, J., He, X., Kankasa, C., West, J. T., Mitchell, C. D., Ruprecht, R. M., Orti, G. & Wood, C.(2006). Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease. Retrovirology3, 73[CrossRef][Google Scholar]
Zheng, N. N. & Daniels, R. S.(2001). Maintenance of glycoprotein-determined phenotype in an HIV type 1 (pNL43) env gene-cassetting system. AIDS Res Hum Retroviruses17, 1501–1506.[CrossRef][Google Scholar]
Zhou, T., Xu, L., Dey, B., Hessell, A. J., Van Ryk, D., Xiang, S. H., Yang, X., Zhang, M. Y., Zwick, M. B. & other authors(2007). Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature445, 732–737.[CrossRef][Google Scholar]
Zwick, M. B., Labrijn, A. F., Wang, M., Spenlehauer, C., Saphire, E. O., Binley, J. M., Moore, J. P., Stiegler, G., Katinger, H. & other authors(2001). Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol75, 10892–10905.[CrossRef][Google Scholar]