HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity.
Recombinant lentiviral vectors pseudotyped with heterologous HIV-1 envelope glycoproteins allow rapid and accurate measurement of antibody-mediated HIV-1 neutralization. However, the neutralization phenotypes of envelope pseudoviruses have not been directly compared to isogenic replication competent HIV-1. We produced pseudoviruses expressing three different HIV-1 envelope glycoproteins and subcloned the same three env genes into a replication competent NL4-3 molecular clone. For each of the antibodies tested, the neutralization dose-response curves of pseudoviruses and corresponding replication competent viruses were similar. Thus, envelope pseudoviruses can be used to study the anti-HIV-1 neutralizing antibody response. A single passage of replication competent virus derived from 293T cells through peripheral blood mononuclear cells (PBMC) caused a substantial decrease in sensitivity to neutralizing antibodies. This was associated with an increase in average virion envelope glycoprotein content of the PBMC-derived virus. Replication competent HIV-1 and isogenic envelope pseudoviruses have similar neutralization characteristics, but passage into PBMC is associated with decreased sensitivity to neutralization.
Louder
Mark K
MK
Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, NIH, 40 Convent Drive, Bethesda, MD 20892, USA.
Sambor
Anna
A
Chertova
Elena
E
Hunte
Tai
T
Barrett
Sarah
S
Ojong
Fallon
F
Sanders-Buell
Eric
E
Zolla-Pazner
Susan
S
McCutchan
Francine E
FE
Roser
James D
JD
Gabuzda
Dana
D
Lifson
Jeffrey D
JD
Mascola
John R
JR
D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D009500:Neutralization Tests; D010641:Phenotype; D013601:T-Lymphocytes / Q000821:virology; D014759:Viral Envelope Proteins / Q000502:physiology*; D014779:Virus Replication
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014759:Viral Envelope Proteins