RECENT DEVELOPMENTS

Be up to date on your knowledge of Poxviridae!  Here are some interesting findings from the past year.

Since the mid-1990s, the United States government had supported an international effort to eradicate every last trace of variola virus, the causative agent of smallpox. There was a tentative plan to destroy all known stocks of variola virus by June 1999. However, in April of 1999, President Clinton signed a memo calling for a preservation of variola virus in the five WHO-approved high-security labs. Only Russia and the United States are currently known to possess cultures of variola. However, some experts allege that not all variola stocks have been accounted for.
According to a White House security official, the decision to preserve the live virus was for its use in developing new anti-viral drugs and testing improved smallpox vaccines. What do you think? Should small-pox be preserved? Wed love to hear what you think. Email us at jaguayo@leland.stanford.edu or jcal@leland.stanford.edu.

Reference: Marshall, E. "President Revokes Plan to Destroy Smallpox" Science 30 Apr 1999 284(5415):718-719.

In June 1999, a working group from the Center for Civilian Biodefense Studies at the School of Public Health, John Hopkins University issued a comprehensive report on recommendations for measures to be taken by medical and public health officials following use of smallpox as a biological weapon. The research group consisted of 21 representatives from major medical centers, research, government, military, public health, and emergency management institutions and agencies. The report issued included specific recommendations regarding smallpox vaccination, therapy, postexposure infection control, hospital epidemiology, and home care. In the event of an actual release of smallpox virus and subsequent outbreaks, early detection, isolation of infected individuals, surveillance of contacts, and an effective vaccination program will be absolutely vital to successful epidemiological control of smallpox. For a more detailed version of the groups report, please see reference below.

Reference: Henderson, DA et al. "Smallpox as a Biological Weapon: Medical and Public Health Management" Journal of the American Medical Association.  9 Jun 1999 281 (22): 2127-37.

The replication kinetics of tanapoxvirus were understood this year by growth of tanapox virus in owl monkey kidney cells. Virus replication revealed production of cytopathic effect, characterized by densely packed rounded cells with granular, vacuolated cytoplasm. An important feature of tanapoxvirus multiplication is that most of the mature progeny is retained inside the cell. The results of this study suggest that tanapoxvirus, in terms of replication kinetics, is very similar to other poxviruses. However, the virus is much slower in replication than vaccinia virus. For more details of this study, please see reference below.

Reference: Mediratta, S. and K. Essani "The replication cycle of tanapox virus in owl monkey kidney cells" Canadian Journal of Microbiology. Jan 1999 45 (1): 92-96.

The development of vaccines for various pathogens using vaccinia virus as a vector has recently sparked significant interest. Cancer research is one such field that has looked into the possibility of using vaccinia virus in the development of vaccination strategies that would give rise to strong tumor-specific responses in cancer patients. One strategy, discovered this year, consisted of using a well-defined human melanoma tumor system to check the possibility of translating the immunological potency of synthetic tumor antigenic peptide analogues into recombinant vaccinia viruses carrying constructs with appropriate nucleotide substitutions. The results of this study indicated that use of these constructs directed the expression of modified melanoma tumor antigens, which then led to improved antigen recognition, and thus, to enhanced immunogenicity. Recombinant vaccinia viruses containing mutated sequences may lead to new strategies for the induction of strong tumor specific responses in cancer patients.

Reference: Valmori, D. et al "Induction of potent antitumor CTL responses by recombinant vaccinia encoding a melan-A peptide analogue" Journal of Immunology. 15 Jan 2000 164(2): 1125-31.

Poxviruses are known to encode several cytokine response modifying (Crm) proteins. The Crm proteins possess sequence homology to several human proteins important in immunity. This homology and the conservation of Crm proteins among poxvirus strains suggests an immunomodulatory function that provides a survival advantage to the virus. It was recently discovered that cowpox virus encodes several tumor necrosis factor (TNF) receptors. The researcher of this study have suggested that understanding the role that these TNF receptors play in altering host immune reponses may lead to the development of specific anti-inflammatory therapeutics.

Reference: Cunnion, K.M. "Tumor necrosis factor receptors encoded by poxviruses."  Molecular Genetics and Metabolism Aug 1999 67 (4): 278-82.

In recent years, vaccinia virus and other poxviruses have been found to express a collection of proteins that can block parts of the host immune response. A recent study found several types of these proteins that bind to interleukin-1, type 1 interferons, and chemokines and are secreted from cells infected with vaccinia virus. The study of immune modulation by proteins such as these can shed light on the understanding of viral pathogenesis and interaction with the immune system. This can in turn have potential application in the treatment of immunological disorders caused by infectious agents.

Refernce: Smith, G.L., J.A. Symons, A. Alcami "Immune modulation by proteins secreted from cells infected by vaccinia virus."  Archives of Virology Supplementum, 1999 15: 111-29.

A chemokine cell receptor, MC 148, encoded by human molluscum contagiosum virus was recently found to block the action of I-309 chemokine on CCR 8. This resulted in interference with monocyte invasion and dendrite cell function. The discovery of the function of MC148 protein could be a useful tool for better understanding the role that CCR 8 plays in the immune system. This study reinforces the idea that by understanding more about the function of viral proteins, we can learn more about how the immune system functions.

Reference: Luttichau, B.H. et al. "A highly selective CC chemokine receptor encoded by the poxvirus molluscum contagiosum."  Journal of Experimental Medicine3 Jan 2000 191(1): 171-80.

Fourteen orthopoxvirus strains isolated from human subjects, cats, a dog, and an elephant were studied in 1999 in Germany. A detailed comparison of these strains demonstrated a close relationship between all of them and confirmed that they were all cowpox viruses. Some differences were detected and this was significant for their epidemiological value. This study helps us better understand the host range of cowpox, despite its misleading name.

Reference: Meyer, H., C. Schay, H. Mahnel, and M. Pfeffer. "Characterization of orthopox virus isolated from man and animals inGermany."  Archives of Virology 1999 144 (3): 491-501.

A neucrotizing pneumonia was observed in a domestic cat which had no clinical history of severe respiratory distress. Electronmicroscopy and immunohistology revealed infection by cowpox virus from the genus Orthpoxvirus. This confirms reports of zoonosis of cowpox virus from infected cats, which seems to be the leading cause of human infection with cowpox.

Reference: Hinrichs, U., H. Van de Poel, and T.S. Van den Ingh "Necrotizing pneumonia in a cat caused by an orthopoxvirus."  Journal of Comparative Pathology Aug 1999 121 (2): 191-6.

A recent study found that the A-type inclusion bodies characteristic of poxviral infections are generated by endoribonucleolytic cleavage at a specific site in the primary transcript. The 3 end of late mRNAs of the ati gene are responsible for encoding these inclusion bodies. For more detailed information on the sequencing of these mRNAs please see reference below.

Reference: Howard, S.T., C.A Ray, D.D. Patel, J.B. Antczak, and D.J. Pickup "A 43-nucleotide cis-acting element governs the site-specific formation of the 3' end of a poxvirus late mRNA."  Virology 1 Mar 1999 225(1): 190-204.

 

 

 

Intro | Recent Developments

Smallpox | Vaccinia| Cowpox | Molluscum Contagiosum | Monkeypox | Tanapox

Pathogen Cards | Antiviral Drugs | Updated References | Helpful Web Links