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NIH Annual Report AI000979

NIH Annual Intramural Research Report

ZIA AI000979-16

Report Title

Poxvirus host interactions, pathogenesis and immunity

2021 Fiscal Year

October 01, 2020 - September 30, 2021

Principal Investigator
 Bernard Moss, MD, PhD

Research Organization

Genetic Engineering Section

Lab Staff and Collaborators within the Genetic Engineering Section
Tatiana Georgia Koonin, PhD
Ruikang Liu, PhD
Patricia Earl, PhD
Jeffrey L Americo, MS
Catherine Griffin
Andrea S Weisberg, MS
Wei Xiao

Collaborators from other NIH organizations

There were 3 NIH collaborators from other Institutes/Centers
Eugene Victor Koonin, PhD NLM
Yuri Igorevich Wolf, PhD NLM
Nataliya Yutin, PhD NLM

External Collaborator

There was one External Collaborator
Paul Gershon, PhD University of California, Irvine, Molecular Biology and Biochemistry

Keywords

cowpox virus pathogenesis, poxvirus immunity, smallpox vaccine, monkeypox virus pathogenesis, orthopoxvirus pathogenesis, poxvirus pathogenesis, vaccinia virus pathogenesis, cell mediated immunity, cytokines, monoclonal antibodies

Goals and Objectives

The goals of this project are to increase our understanding of poxvirus host interactions, pathogenesis and the basis for immunity to poxviruses. We are particularly interested in the members of the orthopoxvirus genus, which include variola virus (the causal agent of smallpox), vaccinia virus (used as the smallpox vaccine), cowpox virus (causes zoonotic infections) and monkeypox virus (causes of human monkeypox in parts of Africa).

Summary

Poxviruses comprise a large family of complex DNA viruses that have vertebrate and invertebrate hosts. Two poxviruses, variola virus and molluscum contagiosum virus, are specific human pathogens. Variola virus was the cause of smallpox until the latter was eradicated but is still feared because of potential use a biological weapon. Molluscum contagiosum virus causes benign skin lesions in immunocompetent infants and a more severe and widespread disease in immunodeficient adults. In addition, several animal poxviruses can be transmitted to humans as zoonosis. The most serious of these is monkeypox, which has an estimated human mortality of 1 to 10%. The poxviruses express a large number of host immune evasion genes that contribute to virulence. The purpose of this project is to increase our understanding of poxvirus host interactions, pathogenesis and the basis for immunity to poxviruses. Human genome-wide RNAi screen was conducted to determine host factors that impact poxvirus replication.

During the past year we took advantage of the 235 available unique complete genome sequences of Orthopoxviruses (ORPV) and reannotated the approximately 200 genes of each to provide the first uniform gene nomenclature. We focused on the approximately 100 accessory genes, predicting the functions of uncharacterized genes, and reconstructed the history of their gain and loss during
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