Fig. 1

Estimation of the relative contribution of putative cell classes defined by reversible inhibition (latent infection) or irreversible blocks (defective infection) of different stages of HIV expression to the total pool of HIV-infected cells in ART-treated individuals. (A) HIV-infected cells that do not transcribe any CA RNA species due to the lack of transcription initiation factors, chromatin organization, epigenetic modifications, etc. (latent infection), or sequence defects in the LTR promoter, Tat-TAR defects, etc. (defective infection). (B) Cells that contain abortive transcripts and low levels of US RNA in the nucleus (which may be incomplete) but no MS RNA and no HIV proteins, due to either lack of factors necessary for transcription elongation or splicing (latent infection), or deletions and splice site mutations (defective infection). (C) Cells that contain low levels of MS RNA, as well as intermediate levels of US RNA, some of which can be transported to the cytoplasm, and a limited set of HIV proteins, due to either low levels of splicing or nuclear export factors (latent infection), or deletions, hypermutation, and mutations in splicing enhancer sequences or in Rev response element (defective infection). (D) Cells that contain high levels of both US and MS RNA but express a limited set of HIV proteins, due to either inhibition of HIV translation by microRNAs or other host factors (latent infection), or deletions, frameshift mutations, and premature stop codons (defective infection). (E) Cells that contain high levels of both US and MS RNA and express the complete set of correct viral proteins but do not produce infectious particles due to either inhibition of particle assembly/maturation by host defense (latent infection), or mutations in the packaging signal (defective infection). (F) Cells that are productively infected. Note that the relative contributions of these cell classes to the total pool of HIV-infected cells, as well as the relative contributions of latent versus defective infection to each class, are rough estimates that are expected to differ substantially from patient to patient and might change over time on therapy, and other cell classes might be present