Monkeypox virus and insights into its immunomodulatory proteins

Abstract

Monkeypox is a disease that is endemic in Central and Western Africa. However, in 2003, there was an outbreak in the United States, representing the first documented monkeypox cases in the Western hemisphere. Although monkeypox virus is less fatal and not as transmissible as variola virus, the causative agent of smallpox, there is concern that monkeypox virus could become a more efficient human pathogen. The reason for this may lie in the virus' genetic makeup, ecological changes, changes in host behavior, and the fact that with the eradication of variola virus, routine smallpox vaccination is no longer carried out. In this review, we focus on the viral proteins that are predicted to modulate the host immune response and compare the genome of monkeypox virus with the genomes of variola virus and the vaccinia virus, the orthopoxvirus that represented the smallpox vaccine. There are differences found in several of these immune-modulating genes including genes that express proteins that affect cytokines such as interleukin-1, tumor necrosis factor, and interferon. There are also differences in genes that code for virulence factors and host range proteins. Genetic differences likely also explain the differences in virulence between two strains of monkeypox virus found in two different regions of Africa. In the current setting of limited smallpox vaccination and little orthopoxvirus immunity in parts of the world, monkeypox could become a more efficient human pathogen under the right circumstances.

Fig. 1. Monkeypox rash

African woman with classical rash of monkeypox virus infection with deep seeded lesions on face, arms, and palms. Photos courtesy of the UCLA Monkeypox Project, Democratic Republic of Congo.

Fig. 2. Phylogenetic tree of different orthopoxvirus species, strain, or isolate based on nucleic acid sequence alignment

The circled portion of the tree represents the comparison of the genomes between three isolates of the West African strain and one isolate of the Central African strain of monkeypox virus (MPXV). The core regions of the genomes were used in each comparison with differences in nucleic acid sequence shown by varying branch length. CMLV: camelpox virus; CPXV: cowpox virus; ECTV: ectromelia virus; MPXV: monkeypox virus; RPXV: rabbitpox virus; VACV: vaccinia virus; VARV: variola virus. Adapted from (19) and reprinted with permission from Elsevier.