A highly unusual v1 region of env in an elite controller of HIV infection

Zachary A. Silver, Gordon Dickinson, Michael S. Seaman, Ronald Charles Desrosiers

Research output: Contribution to journalArticle

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Abstract

HIV elite controllers represent a remarkable minority of patients who maintain normal CD4+ T-cell counts and low or undetectable viral loads for decades in the absence of antiretroviral therapy. To examine the possible contribution of virus attenuation to elite control, we obtained a primary HIV-1 isolate from an elite controller who had been infected for 19 years, the last 10 of which were in the absence of antiretroviral therapy. Full-length sequencing of this isolate revealed a highly unusual V1 domain in Envelope (Env). The V1 domain in this HIV-1 strain was 49 amino acids, placing it in the top 1% of lengths among the 6,112 Env sequences in the Los Alamos National Laboratory online database. Furthermore, it included two additional N-glycosylation sites and a pair of cysteines suggestive of an extra disulfide loop. Virus with this Env retained good infectivity and replicative capacity; however, analysis of recombinant viruses suggested that other sequences in Env were adapted to accommodate the unusual V1 domain. While the long V1 domain did not confer resistance to neutralization by monoclonal antibodies of the V1/V2-glycan-dependent class, it did confer resistance to neutralization by monoclonal antibodies of the V3-glycan-dependent class. Our findings support results in the literature that suggest a role for long V1 regions in shielding HIV-1 from recognition by V3-directed broadly neutralizing antibodies. In the case of the elite controller described here, it seems likely that selective pressures from the humoral immune system were responsible for driving the highly unusual polymorphisms present in this HIV-1 Envelope. IMPORTANCE Elite controllers have long provided an avenue for researchers to reveal mechanisms underlying control of HIV-1. While the role of host genetic factors in facilitating elite control is well known, the possibility of infection by attenuated strains of HIV-1 has been much less studied. Here we describe an unusual viral feature found in an elite controller of HIV-1 infection and demonstrate its role in conferring escape from monoclonal antibodies of the V3-glycan class. Our results suggest that extreme variation may be needed by HIV-1 to escape neutralization by some antibody specificities.

Original languageEnglish (US)
Article numbere00094-19
JournalJournal of Virology
Volume93
Issue number10
DOIs
StatePublished - May 1 2019

Fingerprint

HIV infections
Human immunodeficiency virus 1
HIV Infections
HIV-1
neutralization
monoclonal antibodies
polysaccharides
Polysaccharides
Monoclonal Antibodies
viruses
Viruses
therapeutics
glycosylation
Antibody Specificity
viral load
HIV long-term survivors
sulfides
neutralizing antibodies
CD4 Lymphocyte Count
Neutralizing Antibodies

Keywords

  • BNAb
  • Elite controller
  • HIV-1
  • V1 domain

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

A highly unusual v1 region of env in an elite controller of HIV infection. / Silver, Zachary A.; Dickinson, Gordon; Seaman, Michael S.; Desrosiers, Ronald Charles.

In: Journal of Virology, Vol. 93, No. 10, e00094-19, 01.05.2019.

Research output: Contribution to journalArticle

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