Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are genetically distinct viruses that each can cause AIDS. SIV that infects greater spot-nosed monkeys. It is thought that perhaps recombination occurred in chimpanzees dually infected with SIV that infects red-capped mangabeys and SIV that infects greater spot-nosed monkeys to generate a novel chimeric virus, SIVcpz. Dual infection of distinct lentiviruses, namely, HIV-1 and HIV-2, also occurs in certain human populations. Although HIV-1 and HIV-2 can both cause AIDS (7, 12), these viruses originated from two different SIVs that were transmitted to humans by independent zoonotic events (44). The precursors of HIV-1 and HIV-2 are genetically distinct SIVs that inhabit different natural hosts: HIV-1 is from SIVcpz, whereas HIV-2 is from SIV that infects sooty mangabeys in nature (24). Currently, HIV-1 infection is distributed worldwide, with an estimated 40 million people infected. The distribution of HIV-2 is more limited and is located mostly in West Africa and parts of India (29, 32). Most of the geographic regions that have prevalent HIV-2 infections also have an Vorapaxar novel inhibtior HIV-1 epidemic. Infection by one of the AIDS viruses does not protect the host from the other virus (45); therefore, coinfection is not infrequent in certain geographic areas (21, 22). It was estimated that 1 million people are dually infected with these two viruses (3). Additionally, HIV-1 and HIV-2 use the same receptor and coreceptors for entry into cells (25, 38, 43) and thus target the same cell populations in the host. These properties suggest that in the dually infected population, it is likely that some cells can be infected by both HIV-1 and HIV-2, thereby providing opportunities for these two viruses to interact with each other. HIV-1 and HIV-2 have similar genetic structures; however, they exhibit significant sequence variation. For example, the two virus strains used in this study contain only 55% nucleotide sequence identity in the viral genome and 54%, 55%, and 35% amino acid sequence identity in mutants can complement each other’s function to rescue virus replication; furthermore, the Gag proteins from these two viruses can coassemble into the same virion (8). Gag proteins interact with viral RNA to specifically encapsidate full-length viral RNA into virions (6, 35). The coassembly of HIV-1 and HIV-2 Gag suggests that HIV-1 and HIV-2 RNAs can be copackaged into the same virus particles. If copackaging occurs, it is possible for recombination to take place during reverse transcription, which could generate a chimeric viral genome. In this report, we sought to determine the genetic interactions between HIV-1 and HIV-2. We first examined whether HIV-1 and HIV-2 RNAs can be copackaged into the same virus particle by examining whether recombination can occur between a marker gene encoded by an HIV-1 vector and that encoded by an HIV-2 vector. After observing such events, we then examined whether recombination can occur in the viral genome of these two viruses and found that these recombination events do occur, albeit at low frequencies. These results reveal the potential and the barriers to recombination between genetically distinct viruses and provide insights into retroviral evolution, including the pathogens causing the current AIDS epidemic. MATERIALS AND METHODS Plasmids Vorapaxar novel inhibtior used in the study. HIV-1-based vectors pON-H0 and pON-T6 were described previously (41). Quickly, these vectors had been produced from pNL4-3 and bring practical genes. Each vector consists of two Vorapaxar novel inhibtior marker genes put into includes a substitution and a +1 inactivating frameshift, which can be Rabbit polyclonal to KBTBD8 603 bp through the translation begin site. The reversion prices for both these inactivating mutations are approximated to become suprisingly low (26, 36) and surpass the level of sensitivity of our assay. For clearness, pON-H0 is known as 1-H0G, whereas pON-T6 is known as 1-T6G. HIV-2-centered pHIV2-H0G and pHIV2-T6G had been previously referred to (11) and had been produced from HIV-2 Pole-12. These vectors consist of practical genes. Additionally, they support the same markers and mutations in as the HIV-1 vectors: for HIV-2-H0G using the above-mentioned inactivating mutation 15 bp through the translational begin codon as well as for HIV-2-T6G using the above-mentioned inactivating mutation 603 bp through the translational begin codon. For clearness, pHIV2-T6G and pHIV2-H0G are known as 2-H0G and 2-T6G, respectively. Plasmid pIIINL(Advertisement8)env, a sort or kind present from Eric Freed, was produced from the Advertisement8 strain.