Journal article
The Selection of Low Envelope Glycoprotein Reactivity to Soluble CD4 and Cold during Simian-Human Immunodeficiency Virus Infection of Rhesus Macaques
Journal of virology, Vol.88(1), pp.21-40
01/2014
DOI: 10.1128/JVI.01558-13
PMCID: PMC3911730
PMID: 24131720
Abstract
Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that favor
in vivo
persistence, we inoculated rhesus macaques with three closely related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in ER to cold (ER
cold
) and ER to sCD4 (ER
sCD4
); these SHIVs were neutralized by antibodies equivalently and thus were similar in ER
antibody
. All three SHIVs achieved high levels of acute viremia in the monkeys without alteration of their Env sequences, indicating that neither ER
cold
nor ER
sCD4
significantly influences the establishment of infection. Between 14 and 100 days following infection, viruses with high ER
cold
and ER
sCD4
were counterselected. Remarkably, the virus variant with low ER
cold
and low ER
sCD4
did not elicit a neutralizing antibody response against the infecting virus, despite the generation of high levels of anti-Env antibodies in the infected monkeys. All viruses that achieved persistent viremia escaped from any autologous neutralizing antibodies and exhibited low ER
cold
and low ER
sCD4
. One set of gp120 changes determined the decrease in ER
cold
and ER
sCD4
, and a different set of gp120 changes determined resistance to autologous neutralizing antibodies. Each set of changes contributed to a reduction in Env-mediated entry. During infection of monkeys, any Env replication fitness costs associated with decreases in ER
cold
and ER
sCD4
may be offset by minimizing the elicitation of autologous neutralizing antibodies.
Details
- Title: Subtitle
- The Selection of Low Envelope Glycoprotein Reactivity to Soluble CD4 and Cold during Simian-Human Immunodeficiency Virus Infection of Rhesus Macaques
- Creators
- Kathleen McGee - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Division of AIDS, Harvard Medical School, Boston, Massachusetts, USAHillel Haim - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Division of AIDS, Harvard Medical School, Boston, Massachusetts, USABirgit Korioth-Schmitz - Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USANicole Espy - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Division of AIDS, Harvard Medical School, Boston, Massachusetts, USAHassan Javanbakht - Hoffmann-La Roche, Nutley, New Jersey, USANorman Letvin - Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USAJoseph Sodroski - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.88(1), pp.21-40
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JVI.01558-13
- PMID
- 24131720
- PMCID
- PMC3911730
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 01/2014
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083280302771
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