Nicholas M Provine

Publications (2)8.75 Total impact

• Article: The neutralization sensitivity of viruses representing human immunodeficiency virus type 1 variants of diverse subtypes from early in infection is dependent on producer cell, as well as characteristics of the specific antibody and envelope variant.

  Nicholas M Provine, Valerie Cortez, Vrasha Chohan, Julie Overbaugh
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  ABSTRACT: Neutralization properties of human immunodeficiency virus (HIV-1) are often defined using pseudoviruses grown in transformed cells, which are not biologically relevant HIV-1 producer cells. Little information exists on how these viruses compare to viruses produced in primary lymphocytes, particularly for globally relevant HIV-1 strains. Therefore, replication-competent chimeras encoding envelope variants from the dominant HIV-1 subtypes (A, C, and D) obtained early after infection were generated and the neutralization properties explored. Pseudoviruses generated in 293T cells were the most sensitive to antibody neutralization. Replicating viruses generated in primary lymphocytes were most resistant to neutralization by plasma antibodies and most monoclonal antibodies (b12, 4E10, 2F5, VRC01). These differences were not associated with differences in envelope content. Surprisingly, the virus source did not impact neutralization sensitivity of most viruses to PG9. These findings suggest that producer cell type has a major effect on neutralization sensitivity, but in an antibody dependent manner.
  Virology 02/2012; 427(1):25-33. · 3.35 Impact Factor
• Article: The infectious molecular clone and pseudotyped virus models of human immunodeficiency virus type 1 exhibit significant differences in virion composition with only moderate differences in infectivity and inhibition sensitivity.

  Nicholas M Provine, Wendy Blay Puryear, Xueling Wu, Julie Overbaugh, Nancy L Haigwood
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  ABSTRACT: Two frequently employed methods for generating well-characterized, genetically defined infectious human immunodeficiency virus type 1 in vitro include the use of infectious molecular clones (IMCs) and pseudoviruses (PVs) competent for single-round infection. We compared six matched pairs of IMCs and PVs. The relative amounts of Env incorporated and efficiency of cleavage differed substantially between the two systems. Altering the ratio of proviral genome and env expression plasmids can produce pseudovirions that are structurally more similar to the matched IMCs. Differences in Env incorporation and cleavage translated into moderate differences in assays infectivity and sensitivity to neutralizing antibodies and entry inhibitors.
  Journal of Virology 07/2009; 83(17):9002-7. · 5.40 Impact Factor