First Description of Seronegative HTLV-1 Carriers in Argentina

Abstract

In some areas of Argentina endemic for human T-lymphotropic virus type 1 (HTLV-1), tropical spastic paraparesis is frequent in subjects who lack antibodies against the virus; however, the relevance of this seronegative status in the country has not been investigated. In neighboring countries, HTLV-1 seronegative status has been described in patients with different diseases; however, data regarding features of seronegative HTLV-1 carriers are scarce. We investigated the seronegative status in 124 relatives of 28 HTLV-1 infected subjects from an endemic area in Northwest Argentina. Blood samples and clinical/epidemiological data were collected. Human T-lymphotropic virus type 1 infection was diagnosed by serology and long terminal repeat (LTR) sequence, env and tax gene detection. IgG anti-Tax HTLV-1 antibody, tax gene sequence, and DNA proviral load were also evaluated. Seventy-five percent of the 124 relatives were negative for HTLV-1/2 antibodies; 35.5% were also negative by molecular assays and 64.5% were negative for HTLV-1 LTR and env sequences, but positive for two sequences of HTLV-1 tax gene. Also, 35.7% of these subjects had IgG anti-Tax antibodies. The seronegative HTLV-1 status was significantly associated with male gender, youth, and sensory symptoms/autonomic nervous system dysfunction. High rates of seronegative symptomatic and asymptomatic HTLV-1 carriers in Argentina are described. The evidence highlights that HTLV-1 prevalence may be underestimated worldwide. Larger cohort studies are required to assess disease outcome in these seronegative subjects. Also, the findings emphasize the limitations of ongoing screening assays for diagnosis and blood safety. Therefore, algorithms for HTLV-1 diagnosis should include not only serological but also molecular assays.

Figure 1.

Nucleotide sequence of 1004 bp of the tax gene from Argentinean human T-lymphotropic virus type 1 (HTLV-1) seronegative ArJ03-06 (MK638973); ArJ13-01 (MK638974); ArJ24-01(MK638975); ArJ25-05(MK638976); ArJ26-02(MK638977); ArJ26-04(MK638978); ArJ41-03(MK638979); ArJ44-02(MK638980) and seropositive ArJ03-04 (DQ227152); ArJ19-03 (DQ227166); ArJ32-01 (DQ227174); ArJ48-01 (DQ227186); ArJ65-02 (DQ227191) subjects. Dots represent residues that are identical to ATK. The first and last residues in the HTLV-1 tax gene are provided as well as their position in the ATK genome. The arrow indicates nucleotide changes at the positions 7920, 7982, 8002, 8230, and 8295 compared with HTLV-1 prototype clone ATK-1.

Figure 2.

Optical density (OD) of IgG Anti-Tax human T-lymphotropic virus type 1 (HTLV-1) antibodies detected by ELISA in HTLV-1 seropositive and HTLV-1 seronegative infected subjects. The gray area represents the cutoff (OD = 0.371) of the assay. This figure appears in color at www.ajtmh.org.

Figure 3.

Correlation between IgG anti-Tax reactivity and human T-lymphotropic virus type 1 (HTLV-1) DNA proviral load in seropositive (A) and seronegative (B) HTLV-1 infected groups.