Comparison of tissue distribution, persistence, and molecular epidemiology of parvovirus B19 and novel human parvoviruses PARV4 and human bocavirus

Abstract

Background: PARV4 and human bocavirus (HBoV) are newly discovered human parvoviruses with poorly understood epidemiologies and disease associations. We investigated the frequencies of persistence, tissue distribution, and influence of immunosuppression on replication of these viruses.

Methods: At autopsy, bone marrow, lymphoid tissue, and brain tissue from human immunodeficiency virus (HIV)-infected individuals with acquired immunodeficiency syndrome (AIDS) and those without AIDS and from HIV-uninfected individuals were screened for parvovirus B19, PARV4, and HBoV DNA by means of quantitative polymerase chain reaction analyses.

Results: B19 DNA was detected both in HIV-infected study subjects (13 of 24) and in HIV-uninfected study subjects (8 of 8), whereas PARV4 DNA was detected only in HIV-infected study subjects (17 of 24). HBoV DNA was not detected in any study subjects. The degree of immunosuppression with HIV infection did not influence B19 or PARV4 viral loads. B19 or PARV4 plasma viremia was not detected in any study subjects (n=76; viral load <25 DNA copies/mL). A significantly older age distribution was found for study subjects infected with B19 genotype 2, compared with those infected with B19 genotype 1. Two genotypes of PARV4 were detected; study subjects carrying prototype PARV4 (genotype 1) were younger (all born after 1958) than those infected with genotype 2 (PARV5; study subjects born between 1949 and 1956).

Conclusions: Tight immune control of replication of B19 and PARV4 was retained despite profound immunosuppression. Recent genotype replacement of PARV4, combined with absent sequence diversity among genotype 1 sequences, suggests a recent, epidemic spread in the United Kingdom, potentially through transmission routes shared by HIV.

Table 1.

Clinical background of study subjects.

Table 2.

Frequency of detection of parvovirus B19, human bocavirus (HBoV), and PARV4 in autopsy tissue.

Figure 1.

Viral loads for parvoviruses B19 (A) and PARV4 (B) in different tissues from the study subjects, plotted on a log scale (y-axis). Bars indicate median values for positive samples (filled circles). The significance of the differences in viral loads between subject categories was calculated by use of the Mann-Whitney U test.

Figure 2.

Age ranges for study subjects infected with different genotypes of parvoviruses B19 (A) and PARV4 (B). Open circles, HIV-uninfected study subjects; filled circles, HIV-infected study subjects. Bars indicate median values. The significance of the differences in age range between genotypes of B19 and PARV4 was calculated by use of the Mann-Whitney U test.