Lyssavirus

1
Lyssavirus Tifanie Ernau

• Background and Significance
• Rabies had been known for over 4,000 years
• Pasteur created vaccine for Rabies in 1808 via
  serial passages through rabbits
• Rabies is typically transmitted through animals
  bits (dogs, raccoons, bats)
• Causes acute encephalitis and is fatal without
  prophylaxis.
• Virus enters via direct contact and travels via
  the peripheral and central nervous system to the
  brain where it undergoes fast replication and
  then travels to the salivary glands
• Incubation period 2 weeks to 2 years
• In the US wild animals act as reservoirs (90 of
  all rabies cases reported)
• Dog vaccination programs in the 40s resulted in
  rapid decline of rabies cases
• Rabies is still extremely prevalent in
  underdeveloped countries

• Biology of Virus
• Enveloped (-)ssRNA 11Kbp
• Virus enter via g-protein mediated fusion to host
  membrane and endosomal vesicle
• 5 monocystronic mRNAs produced with 5caps and
  poly A tails
• Encode for L and P proteins necessary for
  transcription, N nucleocapsid, G glycoprotein, M
  matrix protein
• Replication and primary assembly in cytoplasm
  (Negri Body)
• Virions bud from cell membrane with G proteins on
  outside or via synapses

• Future Directions
• Movement through axon
• How virus moves through synapse junctions
• Reducing worldwide incidence

References 1. Bouzamondo E, Ladogana A, Tsiang
H. Alteration of potassiumevoked 5-HT release
from virus-infected rat cortical
synaptosomes. Neuroreport 1993 4 55558. 2
Center for Disease Control. Rabies Home.
http//www.cdc.gov/ncidod/dvrd/rabies/the_virus/vi
rus.html. April 2, 2006. 3 Centers for Disease
Control. Human rabies prevention United States,
1999 recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR Morb
Mortal Wkly Rep 1999 48 121. 4 Centers for
Disease Control. Rabies in a laboratory worker
New York. MMWR Morb Mortal Wkly Rep 1977 26
18384. 5 Centers for Disease Control. Rabies in
a laboratory worker New York. MMWR Morb Mortal
Wkly Rep 1977 26 24950. 6 Charles E.
Rupprecht. Rhabdoviruses Rabies Virus.
http//gsbs.utmb.edu/microbook/ch061.html. April
2, 2006. 7 Conzelmann, K. K. Nonsegmented
negative-strand RNA viruses genetics and
manipulation of viral genomes. Annu. Rev. Genet
1998. 32123162. 8 Desmaris N, Bosch A, Salaun
C, et al. Production and neurotropism of
lentivirus vectors pseudotyped with lyssavirus
envelope glycoproteins. Mol Ther 2001 4
14956. 9 Durrheim DN, Speare R, Petzer M.
Rabies post-exposure management in South Africa
a telephonic survey used as a rapid tool for
operational research. Trop Med Int Health 2002
7 45961. 10 Jackson AC. Pathogenesis. In
Jackson AC, Wunner AH, eds. Rabies. San Diego
Elsevier Science, Academic Press, 2002
24582. 11 Lalli G, Schiavo G. Analysis of
retrograde transport in motor neurons reveals
common endocytic carriers for tetanus toxin and
neurotrophin receptor p75NTR. J Cell Biol 2002
156 23339. 12 Lewis P, Fu Y, Lentz TL. Rabies
virus entry at the neuromuscular junction in
nerve-muscle cocultures. Muscle Nerve 2000
23 72030. 13 Tsiang H. Pathophysiology of
rabies virus infection of the nervous system. Adv
Virus Res 1993 42 375412. 14 Veeraraghavan N,
Gajanana A, Rangasami R, et al. Studies on
the salivary excretion of rabies virus by the dog
from Surandai. Pasteur Institute of Southern
India, Coonoor, Scientific Report, 1968. Coonoor
Pasteur Institute of Southern India, 1969
6870. 15 Whitby JE, Heaton PR, Black EM,
Wooldridge M, McElhinney LM, Johnstone P. First
isolation of a rabies-related virus from
a Daubentons bat in the United Kingdom. Vet Rec
2000 147 38588. 16Wandeler AI, Matter HC,
Kappeler A, Budde A. The ecology of dogs and
canine rabies a selective review. Rev Sci Tech
1993 12 5171. 17 Warrell, M. J., and D. A.
Warrell. Rabies and other lyssavirus
diseases. Lancet 2004 363959969. 18 Warrell
MJ. Rabies. In Cook GC, Zumla AI, eds. Mansons
tropical diseases, 21st edn. Edinburgh Saunders,
2003 80721.