Tropism and Properties of the HIV-1 Envelope Glycoprotein in Transmission
The envelope glycoprotein (Env) spikes on transmitting HIV-1 virus particles mediate infection of the first cells in the new host. These Envs must elude host defenses including innate inhibitors and sometimes neutralizing antibodies. They may also direct mechanisms to penetrate epithelial cell barriers to facilitate mucosal transmission.
Prophylactic vaccines that elicit neutralizing antibodies and microbicides need to be designed and optimized to target transmitting viruses. However, it is as yet unclear whether Envs of viruses that successfully transmit carry specific properties or vulnerabilities that can be targeted by such strategies. What we do know is that viruses that use the coreceptor, CCR5, are preferentially transmitted and that early data suggest these viruses primarily infect CD4+ T-cells over macrophages or dendritic cells.
Some transmitted viruses carry Envs with fewer surface sugars and shorter variable loops that usually protect against neutralizing...
KeywordsBreast Milk Neutralize Antibody Virological Synapse Decidua Basalis Epithelial Cell Barrier
The authors wish to acknowledge NIH R01 grants AI089334 and AI097265 that support their research in this area.
- Agace WW, Amara A, Roberts AI, Pablos JL, Thelen M, Uguccioni M, Li XY, Marsal J, Arenzana-Seisdedos F, Delauney T, Ebert EC, Moser B, Parker CM. Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation. Curr Biol. 2000;10:325–8.PubMedCrossRefGoogle Scholar
- Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9:301–9.PubMedCrossRefGoogle Scholar
- Fouda GG, Yates NL, Pollara J, Shen X, Overman GR, Mahlokozera T, Wilks AB, Kang HH, Salazar-Gonzalez JF, Salazar MG, Kalilani L, Meshnick SR, Hahn BH, Shaw GM, Lovingood RV, Denny TN, Haynes B, Letvin NL, Ferrari G, Montefiori DC, Tomaras GD, Permar SR. HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies. J Virol. 2011;85:9555–67.PubMedCrossRefPubMedCentralGoogle Scholar
- Fouda GG, Mahlokozera T, Salazar-Gonzalez JF, Salazar MG, Learn G, Kumar SB, Dennison SM, Russell E, Rizzolo K, Jaeger F, Cai F, Vandergrift NA, Gao F, Hahn B, Shaw GM, Ochsenbauer C, Swanstrom R, Meshnick S, Mwapasa V, Kalilani L, Fiscus S, Montefiori D, Haynes B, Kwiek J, Alam SM, Permar SR. Postnatally-transmitted HIV-1 envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants. Retrovirology. 2013;10:3.PubMedCrossRefPubMedCentralGoogle Scholar
- Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000;100:587–97.PubMedCrossRefGoogle Scholar
- Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008;105:7552–7.PubMedCrossRefPubMedCentralGoogle Scholar
- Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007;131:1059–71.PubMedCrossRefGoogle Scholar
- Powers KA, Ghani AC, Miller WC, Hoffman IF, Pettifor AE, Kamanga G, Martinson FE, Cohen MS. The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study. Lancet. 2011;378:256–68.PubMedCrossRefPubMedCentralGoogle Scholar