Delayed seroconversion to STLV-1 infection is associated with mutations in the pol and rex genes

Abstract

BackgroundSimian T-cell lymphoma/leukemia virus-1 (STLV-1) infection of non-human primates can serve as a model for human T-cell lymphoma/leukemia virus infection.MethodsTwo tantalus and 2 patas monkeys were transfused with intraspecies whole blood infected with STLV-1. Infection was determined by ELISA, western blot and DNA PCR analyses. The entire genome of the STLV-1 Tan 90 strain and some of the STVL-1 Pat74 strain were amplified using over-lapping primer-pairs and subsequently sequenced.ResultsFollowup studies conducted over 2 years indicated that all 4 monkeys remained healthy despite being infected with STLV-1, as determined by PCR, cloning and sequencing analyses. ELISA and Western blot analyses indicated that both patas monkeys seroconverted within 2 months of transfusion, while one tantalus monkey required one year to seroconvert and the other never fully seroconverted. The tantalus monkey which never fully seroconverted, failed to react to HTLV-1 p24 Gag antigen. Sequence analyses indicated that, while unique, the deduced p24 Gag amino acid sequence of the STLV-1 Tan 90 strain used for infection was still highly homologous to the HTLV-1 p24 Gag amino acids present in the ELISA and WB assays. However, a mutation in the pol sequence of STLV-1 Tan 90 encoded a putative stop codon, while a common deletion in the pol/rex regulatory gene causes significant changes in the Pol, and p27 Rex proteins. These same mutations were also observed in the viral DNA of both recipient infected tantalus monkeys and were not present in the STLV-1 Pat 74 strain.ConclusionOur data suggest that seroconversion to STLV-1 infection may be prolonged due to the above mutations, and that compensatory molecular events must have occurred to allow for virus transmission.

Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2 Infection

“…Serological and molecular follow-up of individuals with indeterminate WB results showed that seroconversion in some cases might take several years [60,61]. Furthermore, a study with macaques infected with the simian T-lymphotropic virus 1 associated the late seroconversion with the presence of polymorphisms in the pol and rex genes [62]. Moreover, 10 of 13 samples from HTLV-1/2 mono-infected patients, indeterminate or positive for both HTLV-1 and HTLV-2 by WB, were positive for only HTLV-1 by LAMP and qPCR or PCR-RFLP (Table S2), indicating false-positive results for HTLV-2.…”

Specific pathogen free macaque colonies: a review of principles and recent advances for viral testing and colony management

“…STLV‐1 infected cell lysates and recombinant proteins (e.g., p21e) now are available for serology and have been applied in multiplex serology platforms as well . Seropositive, but not type‐specific, specimens exhibit antibody reactivity to at least one env protein (e.g., gp21, gp46, or gp62/68) and one gag protein (e.g., p19, p24, or p53) . Reactivity to gag gp19‐I and env gp46‐I is specific for HTLV/STLV‐I and reactivity to env gp46‐II is indicative of HTLV/STLV‐II infection.…”

“…Virus isolation in tissue culture is no longer routinely used for definitive diagnosis due to lower sensitivity and time constraints , so PCR is used instead for definitive diagnosis . PCR to detect provirus in PBMC typically targets the tat region, but may alternatively target and amplify env or pol gene sequences . PCR also is useful as a confirmatory test to resolve indeterminate serologic results, or under conditions of delayed seroconversion, particularly due to coinfection with other immunosuppressive viruses such as SIV and SRV .…”

STLV-1 as a model for studying HTLV-1 infection

“…A limited number of reports described STLV-1 inter-simian species transmission [32, 53, 93, 94] (Table 1). In one report and following an unknown mode of transmission, it was shown that baboons accidentally infected with a rhesus macaque STLV-1 virus, developed leukemia/lymphoma at a high frequency [93].…”

“…Finally, another work reported tantalus and patas animals artificially infected with STLV-1 from other species. All animals became infected, as shown by PCR results, even if one stayed seronegative due to mutations in the genome [94]. Why were these pol mutant viruses still able to infect animals remains unexplained.…”