Efficiency of Human Immunodeficiency Virus Type 1 Postentry Infection Processes: Evidence against Disproportionate Numbers of Defective Virions

Abstract

The vast majority of human immunodeficiency virus type 1 particles are claimed to be noninfectious, but there is disagreement as to whether they are defective or simply lack the opportunity to initiate an infection. We have examined the efficiencies of reverse transcription and integration and find that approximately 1 of every 8 virions that initiate reverse transcription form proviruses, a quantity significantly different from the commonly reported ratio of 1 in 1,000. In addition, results from two different infectivity assays demonstrate that the titers are not equivalent to the number of infectious particles. The apparent predominance of noninfectious particles is due to infrequent occurrences of successful virus-cell interactions.

High efficiency of HIV-1 genomic RNA packaging and heterozygote formation revealed by single virion analysis

“…This result was unexpected, given the previous rough estimates of the genome RNA content of virions and the high efficiency of virion formation that occurs in the absence of genome RNA. A recent study indicated that, under optimal conditions, 1 in 8 to 1 in 20 virions can initiate an infection event, despite earlier estimates that a large portion of HIV-1 particles is noninfectious (22). Our results indicate that most of viral particles have full-length viral RNAs and a low efficiency of genomic RNA packaging is not a major contributor to the formation of noninfectious virions.…”

Pol-Specific CD8 + T Cells Recognize Simian Immunodeficiency Virus-Infected Cells Prior to Nef-Mediated Major Histocompatibility Complex Class I Downregulation

“…However, the vast majority of these infecting viral particles have been reported to be noninfectious (22,30). Emerging evidence suggests that this may actually be an overestimation of defective virions and that ϳ1 in 10 viral particles is infectious (39). Even if we assume this higher estimate (1:10), then according to our dose-response analysis, infection with 2 to 10 infectious virions/cell is sufficient for presentation of incoming virion proteins.…”

Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration

“…It has been estimated that more than 90% of the complete linear viral DNAs made in cultured cells are successfully integrated (31,32). However, the fact that both of the CBD-IBD fusions we tested strongly enhanced titer in MEF-KO cells shows that both support efficient integration and high-level expression of the resulting proviruses.…”