Novel poxvirus infection in 2 patients from the United States

Abstract

Background: Some human poxvirus infections can be acquired through zoonotic transmission. We report a previously unknown poxvirus infection in 2 patients, 1 of whom was immunocompromised; both patients had known equine contact.

Methods: The patients were interviewed and clinical information was abstracted from the patients' medical files. Biopsies of the skin lesions were collected from both patients for histopathology, immunohistochemistry, and transmission electron microscopy analysis. Oral and skin swabs were collected from animals with frequent contact with the patients, and environmental sampling including rodent trapping was performed on the farm where the immunosuppressed patient was employed. "Pan-pox and high Guanine-cytosine" polymerase chain reaction assays were performed on patient, animal, and environmental isolates. Amplicon sequences of the viral DNA were used for agent identification and phylogenetic analysis.

Results: Specimens from both human cases revealed a novel poxvirus. The agent shares 88% similarity to viruses in the Parapoxvirus genus and 78% to those in the Molluscipoxvirus genus but is sufficiently divergent to resist classification as either. All animal and environmental specimens were negative for poxvirus and both patients had complete resolution of lesions.

Conclusions: This report serves as a reminder that poxviruses should be considered in cutaneous human infections, especially in individuals with known barnyard exposures. The clinical course of the patients was similar to that of parapoxvirus infections, and the source of this virus is currently unknown but is presumed to be zoonotic. This report also demonstrates the importance of a comprehensive approach to diagnosis of human infections caused by previously unknown pathogens.

Keywords: imiquimod; immunocompromised; parapoxvirus; poxvirus; skin infection.

Figure 1

A, Large 1 to 1.5 cm facial nodules on patient 1 approximately 3 weeks after lesions developed. B, Patient 1’s lesions 14 months after excision and cryotherapy. C, Marble-sized lesion in the web space between the right index finger and the thumb of patient 2 about 3 weeks after the lesion emerged. D, Patient 2’s lesion 3 weeks after excision and cauterization.

Figure 2

A, Photomicrograph of the lesion from patient 2 shows acantholysis, keratinocyte ballooning degeneration, and dermal capillary proliferation. B, Cytoplasmic inclusions are seen within degenerating keratinocytes (arrowheads). C, Immunohistochemistry staining shows parapoxvirus antigens in red within the keratinocytes.

Figure 3

A, Tissue from patient 1 with intracellular poxvirus particles. B, Mature (arrow) and immature (arrowhead) viral particles at higher magnification. Similar findings were seen in micrographs taken of tissue from patient 2 (C and D). L denotes lipids; T denotes tonofilaments.

Figure 4

Phylogenetic tree showing the relationship of viruses isolated from patient 1 (2012_037) and patient 2 (2013_013) to other poxviruses. There was a single-nucleotide change between the patients’ isolates. The phylogenetic tree was constructed from 620 nucleotide sequences of a high-GC polymerase chain reaction amplicon targeting the highly conserved viral RNA polymerase gene. GenBank accession numbers of individual amplicons are listed: patient 1 (KM491712), patient 2 (KM491713), 3 strains of bovine popular stomatitis virus (BPSV 07005, GQ902054.1; BPSV_AR02, AY386265.1; BPSV 07058, GQ902053.1), 4 strains of orf virus (ORFV_NZ2p, AX754989; ORFV_NZ2, DQ184476.1; ORFV_IA82, AY386263.1;ORFV_SA00, AY386264), a red squirrel pox from the United Kingdom (SQRV_UKHE601899), a molluscum contagiosum–like virus from a donkey (MOCV_Donkey JQ269324), 3 pseudocowpox virus strains (PCPV 06025, GQ902049.1; PCPV 08024, GQ902050.1; PCPV 07012, GQ902051.1), a pseudocowpox-like virus from a US deer hunter (PCPV_Deer09001) [6], a sealpox virus (SELV_hiGC,), 3 strains of molluscum contagiosum virus (MOCV_T1, U60315.1; MOCV 08_031, GQ902057; MOCV 09_029), and Nile crocodilepox virus (CROV_Nile, DQ356948.1). The DNA sequences were aligned with the use of the BioEdit and Clustal alignment programs. Phylogenetic analyses were performed with the use of the Bayesian analysis software packages BEAST and BEAUti, version 1.7.5. The analyses ran a Markov chain Monte Carlo chain length of 5 000 000, with a Hasegawa–Kishino–Yano nucleotide substitution model, strict molecular clock, and sampling of every 1000 states. To root the dendrogram, a myxoma virus, MYXV_wel (JX565582) not shown, is used as the outgroup. The 0.02 scale bar denotes the genetic distance in substitutions per site.