Development of neurologic diseases in a patient with primate T lymphotropic virus type 1 (PTLV-1).

Yoshimi Enose-Akahata,Breanna Caruso,Steven Jacobson,Emily Charlip,Benjamin Haner,Bridgette J Billioux,Joan Ohayon,William M Switzer,Raya Massoud,Govind Nair

doi:10.1186/s12977-016-0290-9

Abstract

BackgroundVirus transmission from various wild and domestic animals contributes to an increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 originated from ancient zoonotic transmission from nonhuman primates, although cases of zoonotic infections continue to occur. Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys, and combined are called primate T-lymphotropic viruses (PTLV-1). However, other clinical syndromes typically seen in humans such as a chronic progressive myelopathy have not been observed in nonhuman primates. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following nonhuman primate exposure.ResultsWe performed detailed laboratory analyses on an HTLV-1 seropositive patient with typical HAM/TSP who was born in Liberia and now resides in the United States. Using a novel droplet digital PCR for the detection of the HTLV-1 tax gene, the proviral load in PBMC and cerebrospinal fluid cells was 12.98 and 51.68 %, respectively; however, we observed a distinct difference in fluorescence amplitude of the positive droplet population suggesting possible mutations in proviral DNA. A complete PTLV-1 proviral genome was amplified from the patient’s PBMC DNA using an overlapping PCR strategy. Phylogenetic analysis of the envelope and LTR sequences showed the virus was highly related to PTLV-1 from sooty mangabey monkeys (smm) and humans exposed via nonhuman primates in West Africa.ConclusionsThese results demonstrate the patient is infected with a simian variant of PTLV-1, suggesting for the first time that PTLV-1smm infection in humans may be associated with a chronic progressive neurologic disease.

Highlights

Virus transmission from various wild and domestic animals contributes to an increased risk of emerg‐ ing infectious diseases in human populations
Other causes of chronic myelopathy were excluded: laboratory testing for Lyme antibody, B12, folate, copper, rapid plasma reagin, Human immunodeficiency virus (HIV)-1 and -2, and rheumatology panel were all negative or within normal limits; cerebrospinal fluid (CSF) analysis showed no evidence of malignancy or other infectious etiologies; and magnetic resonance imaging (MRI) showed no evidence of spinal cord compression, tumor, syrinx, or transverse myelitis
We have reported previously that mutations in regions of Human T-cell lymphotropic virus type 1 (HTLV-1) PCR binding probes could be identified using Droplet digital PCR (ddPCR) [19] and exploited this observation when it was apparent that HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient NIH00261 demonstrated a lower fluorescence amplitude of the HTLV-1 tax sequence in both peripheral blood mononuclear cells (PBMCs) and CSF when compared to other HAM/TSP patients

Summary

Introduction

Virus transmission from various wild and domestic animals contributes to an increased risk of emerg‐ ing infectious diseases in human populations. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following nonhuman primate exposure. Virus transmission from various wild and domestic animals has contributed to the increased risk of emerging infectious diseases in human populations. Similar to HTLV-1, most STLV-1-infected monkeys remain asymptomatic, but only a small subset of monkeys develops STLV-associated lymphoma/ leukemia that shares clinical and pathological features with ATL in humans [13, 14]. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following NHP exposures. STLV-1 that cross the species barrier to humans and cause virus-associated neurologic and inflammatory diseases after chronic infection would be of significant public health interest

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