Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.
dc.contributor.author | Barbian, Hannah J | |
dc.contributor.author | Decker, Julie M | |
dc.contributor.author | Bibollet-Ruche, Frederic | |
dc.contributor.author | Galimidi, Rachel P | |
dc.contributor.author | West, Anthony P | |
dc.contributor.author | Learn, Gerald H | |
dc.contributor.author | Parrish, Nicholas F | |
dc.contributor.author | Iyer, Shilpa S | |
dc.contributor.author | Li, Yingying | |
dc.contributor.author | Pace, Craig S | |
dc.contributor.author | Song, Ruijiang | |
dc.contributor.author | Huang, Yaoxing | |
dc.contributor.author | Denny, Thomas N | |
dc.contributor.author | Mouquet, Hugo | |
dc.contributor.author | Martin, Loic | |
dc.contributor.author | Acharya, Priyamvada | |
dc.contributor.author | Zhang, Baoshan | |
dc.contributor.author | Kwong, Peter D | |
dc.contributor.author | Mascola, John R | |
dc.contributor.author | Verrips, C Theo | |
dc.contributor.author | Strokappe, Nika M | |
dc.contributor.author | Rutten, Lucy | |
dc.contributor.author | McCoy, Laura E | |
dc.contributor.author | Weiss, Robin A | |
dc.contributor.author | Brown, Corrine S | |
dc.contributor.author | Jackson, Raven | |
dc.contributor.author | Silvestri, Guido | |
dc.contributor.author | Connors, Mark | |
dc.contributor.author | Burton, Dennis R | |
dc.contributor.author | Shaw, George M | |
dc.contributor.author | Nussenzweig, Michel C | |
dc.contributor.author | Bjorkman, Pamela J | |
dc.contributor.author | Ho, David D | |
dc.contributor.author | Farzan, Michael | |
dc.contributor.author | Hahn, Beatrice H | |
dc.contributor.editor | Goff, Stephen P | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2017-01-03T19:23:19Z | |
dc.date.issued | 2015-04-21 | |
dc.description.abstract | UNLABELLED: Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related simian immunodeficiency viruses (SIVs) infecting central (Pan troglodytes troglodytes) (SIVcpzPtt) and eastern (Pan troglodytes schweinfurthii) (SIVcpzPts) chimpanzees (n = 11) as well as western gorillas (Gorilla gorilla gorilla) (SIVgor) (n = 1). We found that bNabs directed against the CD4 binding site (n = 10), peptidoglycans at the base of variable loop 3 (V3) (n = 5), and epitopes at the interface of surface (gp120) and membrane-bound (gp41) envelope glycoproteins (n = 5) failed to neutralize SIVcpz and SIVgor strains. In addition, apex V2-directed bNabs (n = 3) as well as llama-derived (heavy chain only) antibodies (n = 6) recognizing both the CD4 binding site and gp41 epitopes were either completely inactive or neutralized only a fraction of SIVcpzPtt strains. In contrast, one antibody targeting the membrane-proximal external region (MPER) of gp41 (10E8), functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Ig(mim2), CD4-218.3-E51, and CD4-218.3-E51-mim2), as well as mono- and bispecific anti-human CD4 (iMab and LM52) and CCR5 (PRO140, PRO140-10E8) receptor antibodies neutralized >90% of SIVcpz and SIVgor strains with low-nanomolar (0.13 to 8.4 nM) potency. Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5 and neutralized SIVcpz in chimpanzee CD4(+) T cells, with 50% inhibitory concentrations (IC50s) ranging from 3.6 to 40.5 nM. These findings provide new insight into the protective capacity of anti-HIV-1 bNabs and identify candidates for further development to combat SIVcpz infection. IMPORTANCE: SIVcpz is widespread in wild-living chimpanzees and can cause AIDS-like immunopathology and clinical disease. HIV-1 infection of humans can be controlled by antiretroviral therapy; however, treatment of wild-living African apes with current drug regimens is not feasible. Nonetheless, it may be possible to curb the spread of SIVcpz in select ape communities using vectored immunoprophylaxis and/or therapy. Here, we show that antibodies and antibody-like inhibitors developed to combat HIV-1 infection in humans are capable of neutralizing genetically diverse SIVcpz and SIVgor strains with considerable breadth and potency, including in primary chimpanzee CD4(+) T cells. These reagents provide an important first step toward translating intervention strategies currently developed to treat and prevent AIDS in humans to SIV-infected apes. | |
dc.identifier | ||
dc.identifier | mBio.00296-15 | |
dc.identifier.eissn | 2150-7511 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | American Society for Microbiology | |
dc.relation.ispartof | MBio | |
dc.relation.isversionof | 10.1128/mBio.00296-15 | |
dc.subject | Animals | |
dc.subject | Antibodies, Neutralizing | |
dc.subject | Cross Reactions | |
dc.subject | Gorilla gorilla | |
dc.subject | HIV Antibodies | |
dc.subject | Humans | |
dc.subject | Inhibitory Concentration 50 | |
dc.subject | Neutralization Tests | |
dc.subject | Pan troglodytes | |
dc.subject | Simian Acquired Immunodeficiency Syndrome | |
dc.subject | Simian Immunodeficiency Virus | |
dc.title | Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. | |
dc.type | Journal article | |
duke.contributor.orcid | Parrish, Nicholas F|0000-0002-6971-8016 | |
pubs.author-url | ||
pubs.issue | 2 | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Duke Human Vaccine Institute | |
pubs.organisational-group | Global Health Institute | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.organisational-group | Medicine | |
pubs.organisational-group | Medicine, Duke Human Vaccine Institute | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Staff | |
pubs.organisational-group | University Institutes and Centers | |
pubs.publication-status | Published online | |
pubs.volume | 6 |
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