Frequent horizontal and mother-to-child transmission may contribute to high prevalence of STLV-1 infection in Japanese macaques

Abstract

Background: Simian T-cell leukemia virus type 1 (STLV-1) is disseminated among various non-human primate species and is closely related to human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Notably, the prevalence of STLV-1 infection in Japanese macaques (JMs) is estimated to be > 60%, much greater than that in other non-human primates; however, the mechanism and mode of STLV-1 transmission remain unknown. The aim of this study is to examine the epidemiological background by which STLV-1 infection is highly prevalent in JMs.

Results: The prevalence of STLV-1 in the JMs rearing in our free-range facility reached up to 64% (180/280 JMs) with variation from 55 to 77% among five independent troops. Anti-STLV-1 antibody titers (ABTs) and STLV-1 proviral loads (PVLs) were normally distributed with mean values of 4076 and 0.62%, respectively, which were mostly comparable to those of HTLV-1-infected humans. Our initial hypothesis that some of the macaques might contribute to frequent horizontal STLV-1 transmission as viral super-spreaders was unlikely because of the absence of the macaques exhibiting abnormally high PVLs but poor ABTs. Rather, ABTs and PVLs were statistically correlated (p < 0.0001), indicating that the increasing PVLs led to the greater humoral immune response. Further analyses demonstrated that the STLV-1 prevalence as determined by detection of the proviral DNA was dramatically increased with age; 11%, 31%, and 58% at 0, 1, and 2 years of age, respectively, which was generally consistent with the result of seroprevalence and suggested the frequent incidence of mother-to-child transmission. Moreover, our longitudinal follow-up study indicated that 24 of 28 seronegative JMs during the periods from 2011 to 2012 converted to seropositive (86%) 4 years later; among them, the seroconversion rates of sexually matured (4 years of age and older) macaques and immature macaques (3 years of age and younger) at the beginning of study were comparably high (80% and 89%, respectively), suggesting the frequent incidence of horizontal transmission.

Conclusions: Together with the fact that almost all of the full-adult JMs older than 9 years old were infected with STLV-1, our results of this study demonstrated for the first time that frequent horizontal and mother-to-child transmission may contribute to high prevalence of STLV-1 infection in JMs.

Keywords: Antibody titer; Horizontal transmission; Japanese macaques; Mother-to-child transmission; Prevalence; Proviral load; STLV-1.

Fig. 1

Distribution of anti-STLV-1 antibody titers (ABTs) in seropositive JMs. Distribution of ABTs in all seropositive cohorts JMs (a) and in each troop (b) is indicated. The dotted line shows the detection limit of the ABT (16), and the red line indicates the geometric mean of the ABT distribution

Fig. 2

Distribution of proviral loads (PVLs). Distribution of STLV-1 PVLs in all proviral DNA-positive cohorts JMs (a) and in each troop (b) is shown. The dotted line indicates the detection limit of the PVL (0.01%), and the horizontal line indicates the geometric mean of the PVL distribution

Fig. 3

Correlation between antibody titers (ABTs) and proviral loads (PVLs) among individuals who were positive for either value. Among the JMs (N = 183), 168 were positive for both values, whereas three were seronegative but positive for PVLs, and 12 were seropositive but negative for PVLs. The horizontal and vertical dotted lines show the detection limits of PVL and ABT, respectively, as indicated in Figs. 1, 2. There was a significant correlation between the ABTs and the PVLs (R = 0.50; p < 0.0001)