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

http://www.ncbi.nlm.nih.gov/pubmed/25900654

dc.identifier

mBio.00296-15

dc.identifier.eissn

2150-7511

dc.identifier.uri

https://hdl.handle.net/10161/13347

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

http://www.ncbi.nlm.nih.gov/pubmed/25900654

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

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.pdf
Size:
3.49 MB
Format:
Adobe Portable Document Format