Scientific Publications by FDA Staff

J Virol 2011 Jul;85(13):6579-88

Chemical induction of endogenous retrovirus particles from the vero cell line of african green monkeys.

Ma H, Ma Y, Ma W, Williams DK, Galvin TA, Khan AS

Endogenous retroviral sequences are present in high copy number in the genomes of all species and may be expressed as RNAs, however, the majority are defective for virus production. Although virus has been isolated from various Old World monkey and New World monkey species, there has been no report of endogenous retroviruses produced from African green monkey (AGM) tissues or cell lines. We have recently developed a step-wise approach for evaluating the presence of latent viruses by chemical induction (Khan et al., Biologicals, 37:196-201). Based upon this strategy, optimum conditions were determined for investigating the presence of inducible, endogenous retroviruses in the AGM-derived VERO cell line. Low-level reverse transcriptase activity was produced with 5-azacytidine (AzaC) and with 5' -iodo-2' deoxyuridine (IUdR); none was detected with sodium butyrate. Nucleotide sequence analysis of PCR-amplified fragments from the gag, pol, and env regions of RNAs, prepared from ultracentrifuged pellets of filtered supernatants, indicated that endogenous retrovirus particles related to simian endogenous type D, betaretrovirus sequences (SERV) and to baboon endogenous virus type C gammaretrovirus sequences (BaEV) were induced by AzaC, whereas SERV was also induced by IUdR. Additionally, sequence heterogeneity was seen in the RNAs of SERV- and BaEV-related particles. Infectivity analysis of drug-treated AGM-VERO cells showed no virus replication in cell lines known to be susceptible to type D simian retroviruses (SRVs) and to BaEV. . indicated the presence of several inducible, endogenous retrovirus loci in the AGM genome. The results indicated that multiple, inducible endogenous retrovirus loci are present in the AGM genome that can encode noninfectious, virus-like particles.