Tanapox Virus Research Articles

A secreted high-affinity inhibitor of human TNF from Tanapox virus.

A class of secreted poxvirus tumor necrosis factor (TNF)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TNF-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TNF with high affinity (K(d) = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TNF family members. The 2L protein can inhibit human TNF from binding to TNF receptors I and II as well as block TNF-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TNF and offers a unique strategy with which to modulate TNF activity.

The replication cycle of tanapox virus in owl monkey kidney cells

The growth kinetics of tanapox virus in owl monkey kidney cells was elucidated by single-step growth curves at multiplicities of 10, 1.0, and 0.1 plaque forming units (pfu) per cell at 37 and 33°C. Virus replicated equally well at both temperatures and produced a cytopathic effect that was characterized by densely packed rounded cells with retrogressed monolayer and granular vacuolated cytoplasm. Single-step growth curves revealed that the eclipse period varied from 24 h postinfection (hpi) at a multiplicity of infection of 10 pfu/cell to 48 hpi at 0.1 pfu/cell. The length of the latent period also varied from 36 hpi at 10 pfu/cell to 48 hpi at 0.1 pfu/cell. The intracellular virus, extracellular virus, and total virus titers reached their maximums relatively early at 10 pfu/cell as compared with 0.1 pfu/cell. About 78% of the mature progeny virion is retained intracellularly at 10 pfu/cell at 96 hpi. We conclude that tanapox virus replication is similar to other poxviruses, but the replication cycle is longer when compared with vaccinia virus.Key words: tanapox virus, single-step growth curve, eclipse period, latent period.

The replication cycle of tanapox virus in owl monkey kidney cells.

The growth kinetics of tanapox virus in owl monkey kidney cells was elucidated by single-step growth curves at multiplicities of 10, 1.0, and 0.1 plaque forming units (pfu) per cell at 37 and 33 degrees C. Virus replicated equally well at both temperatures and produced a cytopathic effect that was characterized by densely packed rounded cells with retrogressed monolayer and granular vacuolated cytoplasm. Single-step growth curves revealed that the eclipse period varied from 24 h postinfection (hpi) at a multiplicity of infection of 10 pfu/cell to 48 hpi at 0.1 pfu/cell. The length of the latent period also varied from 36 hpi at 10 pfu/cell to 48 hpi at 0.1 pfu/cell. The intracellular virus, extracellular virus, and total virus titers reached their maximums relatively early at 10 pfu/cell as compared with 0.1 pfu/cell. About 78% of the mature progeny virion is retained intracellularly at 10 pfu/cell at 96 hpi. We conclude that tanapox virus replication is similar to other poxviruses, but the replication cycle is longer when compared with vaccinia virus.

Selective inhibition of TNF-αinduced cell adhesion molecule gene expression by tanapox virus

Poxviruses encode virulence factors that have been identified as proteins that are secreted from infected host cells. Some of these secretory proteins impede host immune defences. We have previously demonstrated that tanapox virus (TPV) infected cells secrete an early 38 kDa glycopeptide that binds to human (h) interferon-γ, hIL-2, and hIL-5. We now show an additional activity in the supernatant from TPV infected cells that down-regulates the expression of tumour necrosis factor-α (TNF-α) induced cell adhesion molecule gene expression. This activity was not detected in mock infected cells. Enzyme linked immunosorbent assays (ELISA) on primary human endothelial cells, show the induction of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) following TNF-α or IL-1β treatment, as expected. Supernatant from TPV infected cells significantly decreased the TNF-α but not IL-1β-induced expression of these molecules. Mobility shift assays and Northern blot analyses further show that the supernatant from TPV infected cells inhibited TNF-α-induced activation of the nuclear transcription factor-κB (NF-κB) and transcriptional activation of the E-selectin, VCAM-1 and ICAM-1 genes. Based on TNF-α affinity chromatography, this activity appears to be associated with a 38 kDa glycopeptide.

Multiple anti-cytokine activities secreted from tanapox virus-infected cells

Tanapox virus (TPV) produces a mild disease in humans characterized by transient fever, one or more nodular skin lesions and regional lymphadenopathy. We demonstrate that TPV-infected cells, but not mock-infected cells, secrete an early 38 kDa glycopeptide that, unlike any other known protein, binds to human (h) interferon-γ, hIL-2 and hIL-5. In concomitant experiments this polypeptide failed to bind to hIL-Iα, hIL-3, hIL-4, hIL-6, hIL-7, hIL-8 or hIL-10. Inhibition of hIL-2 and hIL-5 biological activities were demonstrated using a hIL-2-dependent mouse T cell line (HT-2) and a hIL-5-dependent erythroleukemia cell line (TF-1), respectively. The 38 kDa polypeptide also inhibited the bioactivity of interferon-γ. Taken together, our results suggest that TPV has evolved multiple pathways to disarm both TH1 cell mediated (IL-2 and interferon-γ) and TH2-associated (IL-5) immune responses for its infectivity with remarkable genetic economy.

Studies on tanapox virus

Virus characterization studies were performed to meliorate the taxonomic status of three currently unclassified, serologically related viruses: Tanapox virus (causes vesicular skin lesions in humans), Yaba-like disease (YLD) cirus (causes vesicular skin lesions in monkeys), and Yaba monkey tumor virus (YMTV, causes epidermal histiocytoma). These studies included (1) microscopic observations of Tanapox virus cytopathic effect and morphogenesis during its 6-day cytolytic-type growth at 35° in CV-1 monkey kidney cells; (2) resolution of Tanapox virion proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of nonenveloped and double-enveloped virus particles purified by velocity sedimentation in sucrose and CsCI density gradients; and (3) restriction endonuclease DNA comparison of the three viruses. DNA analysis showed that six recent Tanapox virus isolates from patients in Zaire, Africa, were identical to Tanapox virus, Kenya strain, from 1957 from a patient in the Tana River Valley. In addition, BamHI, MIuI, and PstI cleavage sites mapped on the DNA of Kenya Tanapox virus, and PstI sites mapped on DNA of YLD virus differentiated YLD and Tanapox viruses as separate strains. On the other hand, YMTV shared few restriction endonuclease sites with Tanapox and YLD viruses, although all three cross-hybridized extensively. These studies along with published viral characteristics, support the formation of a new poxvirus genus: the suggested name is Yatapoxvirus, and the genus currently comprises two species, Tanapox virus and YMTV.

Tanapox. A serological survey of the lower Tana River valley

Sera collected from the indigenous population of the Tana River valley during the Tana River Expedition in 1976 were examined for neutralizing antibody to Tanapox virus. Antibody was found in 9.2% of the population in infected areas. This result and the presence of antibody in four children indicated that infection had continued to occur in the area since the 1962 outbreak.

Persistence of tanapox in Tana River valley.

Sera collected from inhabitants of the Tana River valley in 1971 were examined for antibody to tanapox virus. Neutralizing antibody was present in 16.3%. The levels of antibody and its presence in two children under the age of 10 years indicated that infection had been occurring in the area since the reported outbreak in 1962. A comparison of the incidence and distribution of antibodies in the same sera to West Nile virus revealed marked similarities suggesting that tanapox, like West Nile virus infections, might be transmitted in the same way-namely, by a culicine mosquito.

Comparison of Tanapox virus and Yaba-like viruses causing epidemic disease in monkeys.

The virus of Tanapox isolated from the lesions of patients during an outbreak of mild disease in Africa has been found to be indistinguishable in its biological and serological properties from a virus isolated from outbreaks of a pox virus infection in monkeys in primate centres in America. The natural hosts of this virus are believed to be African monkeys and ;Tanapox virus' is proposed as a suitable designation for the virus.

Electron microscopy of the tana poxvirus

The fine structure of Tana virus, a poxvirus originally isolated from children in Kenya, has been studied by electron microscopy of infected rhesus embryonic monkey tissue cultures. The intracytoplasmic maturation of the virus has been analyzed and compared with that seen in Yaba-like disease (Y.L.D.), an epidermal pox disease of monkeys. Two types of virus factories have been distinguished, one of which appears to be responsible for formation of nucleoids, the other for virus membranes. Honeycombed crystals, cylindrical tubules, mitochondria in pairs or triplets, and myelin figures were also observed. The nuclei showed areas of decreased electron opacity. The development of Tana virus was identical with that of Y.L.D. virus. These findings are consistent with the hypothesis, based on serologic studies, that Tana poxvirus is identical with Y.L.D. virus but differs from a similar monkey poxvirus, the Yaba tumor virus.