Viral regulatory region effects on vertical transmission of polyomavirus SV40 in hamsters

Abstract

Viral strain differences influence the oncogenic potential of polyomavirus simian virus 40 (SV40). We hypothesized that viral strain differences might also affect vertical transmission of SV40 in susceptible hosts. Pregnant Syrian golden hamsters were inoculated intraperitoneally with 10(7) plaque-forming units of SV40 and offspring were sacrificed post-delivery (1-21 days, 6 months). Organ extracts were analyzed for SV40 DNA by polymerase chain reaction assay. Transmission of SV40 from mother to offspring was detected in over half of litters. Most placentas were virus-positive. Mothers inoculated with SV40 strains containing complex regulatory regions transmitted virus more frequently than those infected with simple enhancer viruses (p<0.001). Virus was detected more often in progeny brain than in spleen (p<0.05). Several progeny were virus-positive at 6 months of age, suggesting viral persistence. Maternal animals retained virus in several tissues through day 21 and developed T-antigen antibodies. These results indicate that SV40 replicates in hamsters, vertical transmission of SV40 can occur, and the viral regulatory region influences transmission.

Fig. 1

Quantitative assay for hamster vimentin gene. (A) A representative hamster vimentin gene amplification plot of normalized reporter fluorescence (ΔRn) against the cycle number. The log₁₀ of the input copy number of each plasmid standard is indicated. NTC, Non-template control. (B) Typical standard curve for the hamster vimentin gene created by regression analysis of the observed C_T value against the log₁₀ of the input copy number of standard plasmid DNA encoding the vimentin gene sequences. R² = 0.9991; y = 3.3295x + 40.579.

Fig. 2

Regulatory regions of SV40 viral isolates. The viral origin of DNA replication spanning nucleotides 5192 to 31 is represented by the box labeled ORI; the 21-bp repeat region between nucleotides 40 and 103 is shown; the boxed number 72 is the 72-bp sequence within the enhancer region that is duplicated in some laboratory-adapted strains, with the rearranged enhancer region of SVPML-1 represented with boxes labeled 38, 23, 20 and a shaded box referring to nucleotides 252-263. Nucleotide numbers are based on that of SV40-776. Modified from Lednicky and Butel (2001) and Stewart et al. (1998).