Alternative mode of replication of human immunodeficiency virus: a hypothesis

For diagnosis of Human Immunodeficiency Virus (HIV) infection by the recently developed Polymerase Chain Reaction (PCR), the two commonly used clinical samples are either the peripheral blood monocytes (PBMC) or the plasma of the infected individuals. In the former instance, DNA is extracted from PBMC. The integrated proviral DNA is then amplified using HIV specific oligonucleotide primers. In the latter instance, RNA is extracted from plasma. This is reverse transcribed in vitro into cDNA by using extraneous reverse transcriptase. This cDNA is then used as a target in PCR experiments with HIV specific primers. In contrast we have recently used DNA directly extracted from plasma of infected individuals. This DNA was used for amplification of HIV genome with primer pairs specific for HIV. An interesting outcome of this study was a model to explain the presence of DNA of HIV in the plasma. We suggest that possibly there is an alternative mode of replication of HIV. Apart from the obligatory integration of the DNA of HIV into the DNA of lymphocytes as provirus, several additional copies of the DNA are also made which remain unintegrated. These probably exist as a housekeeping repertoire of the viral genome. These DNA molecules may be released into the circulation along with the newly formed mature virion particles during the usual course of replication and release of the virus. In our experiments with direct extraction of DNA from plasma, these unintegrated DNA of HIV may act as the target for PCR to give positive signals with HIV specific primers.