1、Arenavirus,Presented by Sue Y. Hwang,What are the Arenaviridae?,Arenaviridae * A family of viruses whose members are generally associated with rodent-transmitted disease in humans.,Taxonomy,Family: Arenaviridae Genus: Arenavirus Subgroup (2):A) LCM-LASV Complex (Old World Arenaviruses) B) Tacaribe C
2、omplex (New World Arenaviruses),What viruses are included in the virus family?,The arenaviruses are divided into two groups: the New World or Tacaribe complex and the Old World or LCM/Lassa complex. Of the fifteen Arenaviruses known to infect animals, five cause disease in humans: Lassa virus, Junin
3、 virus, Machupo virus, Guanarito virus, and lymphocytic choriomeningitis virus. All arenaviruses contain a set of internal cross-reacting antigens as well as species-specific envelope antigens. Source: http:/www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/arena.htm,Virus Morphology,Spherical An average
4、 diameter of 110-130 nm Enveloped in a lipid membrane. Has grainy particles that are ribosomes acquired from their host cells. (derived from the Latin “arena,“ which means “sandy.“ ) Their genome is composed of RNA only. New viral particles, called virions, are created by budding from the surface of
5、 their hosts cells.,This image shows extracellular virus particles budding from the cell surface. Magnification approx. 12,000 times. Image courtesy Cynthia Goldsmith, MS, Infectious Disease Pathology Activity, DVRD, NCID, CDC.,Genome,Each virion contains multiple copies of genome (multipartite)Viri
6、ons contain 2 % nucleic acid. * Two segments of (RNA L and S) linear negative-sense single stranded RNA.- S encodes the major structure of the virion (NP, GP-1, and GP-2). - L encodes the viral RNA-dependent RNA polymerase (L), and a regulatory protein (Z). Total genome length is 5000-7400 nt.* Each
7、 segment forms a circle by hydrogen bonding of its end. (Nucleotide sequences of 3-terminus largely complementary to similar regions on the 5 end) The hairpin serves as the transcription termination signal. * Genome itself is non-infectious,From Ray Baumann, at the University of Mississippi School o
8、f Medicine,Replication,Replication cycle is not fully understood yet.,Replication continued,Virions attach to undefined receptors and enter host cells.Virus uncoating occurs in the cytoplasm; the viral nucleic acid is delivered to the cell cytoplasm; the site of mRNA Early genes are expressed during
9、 genome uncoating. Transcription of the genome and replication is confined to the cytoplasm.5. Non-structural proteins involved in transcription. -The viral genome is transcribed from the viral sense strand either from the 3 end or from the 5 end- By a viral RNA-dependent RNA polymerase into 2 mRNA(
10、s) (S and L mRNA).,6. The small (S) RNA in the virion encodes - in the negative sense a nucleoprotein (NP)- in the positive or message sense a precursor glycoprotein (GPC), which is cleaved into two virion glycoproteins (GP1 and GP2). The large (L) RNA in the virion encodes-in the negative sense an
11、RNA-dependent RNA polymerase (L)-in the positive sense a zinc-binding protein (Z) which binds to the ribonucleoprotein complex. 7. Specific termination sequences have been identified. Termination is caused by characteristic GC-rich, strongly base-paired stem loop-structure. 8. The virus buds from th
12、e plasma membrane, incorporating host lipids into the virus membrane.,9. Host cells remain intact. Virus is released from host cell by budding through the cell membrane and gain an envelope. Virus is released from host cell without causing death.,Pathogenesis,Chronic infection in rodent host. (Howev
13、er, the viruses do not appear to cause obvious illness in them.) Rodents that carry the Old World arenaviruses can transmit the virus from mother to offspring during pregnancy. Thus, virus remains in the rodent population generation after generation New World arenavirus carrying rodents can only tra
14、nsmit among adult rodents, so only a portion of mice are infected at one time. This leads to cyclic trends in the incidence of human cases.Human infection occurs by contact with rodent excretions Contaminated food Dust with urine (inhale) Exposed woundsSecondary spread (person-person) Nosocomial Con
15、tact with infected blood and other excretions Contact with contaminated medical equipment,Pathogenesis continued,Zoonotic (In nature, the virus is found in animals) Each virus is associated with either one species or a few closely related rodents. EX:1. Tacaribe complex viruses are associated with t
16、he New World rats.2. The LCM/Lassa complex viruses are associated with the Old World rats.,Symptoms,The onset of the hemorrhagic fevers caused by Lassa, Junin, Machupo, and Guanarito viruses: - within 7 to 14 days, -pyrexia-headache-sore throat-myalgiaVirus can be recovered from the blood and serum
17、for up to 3 weeks after onset of the infection.Lassa virus can be recovered from the urine for up to 5 weeks.,Host Defenses,Interferon is induced by Arenavirus infection. Slow humoral response. Cell-mediated immunity is probably of prime importance,Epidemiology,The arenaviruses that affect humans ex
18、ist in nature as benign infections in restricted rodent hosts,Frequent hospital-acquired infections in West Africa brought Lassa virus to the attention of the medical world 25 years ago. It is transmitted at the village level and that most infections are asymptomatic. For those sick enough to be adm
19、itted to the hospital, mortality is about 15 percent. 1. The case fatality rates associated with Junin, Machupo, and Guanarito viruses range from 5 to 35 percent. LCM virus, which is found worldwide in Mus musculus (the common field mouse), is considered to be the agent in about 5 percent of CNS inf
20、ections. These infections are rarely fatal.,Diagnosis,Differential clinical diagnosis is complex; the diagnosis is confirmed only by detecting a rise in antibody titers (IgM, IgG) or by isolating the virus.The traditional methods of diagnosis:-Virus isolation- Virus neutralization- Detection of anti
21、bodies- Polymerase chain reaction technology.,Prevention,Keep food in rodent proof containers Reduce rodent population At a hospital setting Wear protective clothing Sterilize equipment,Treatment,Therapy with ribavirin (anti-viral) is proven to be effective in treating some infections in Africa and
22、South when given early in infection.The sooner treatment is started after infection, the better the chances of survival.,Control,Elimination of rodents is effective but often not practicalVaccines and antiviral agents (e.g., ribavirin) .,Sources,http:/www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/arena.htm http:/ http:/gsbs.utmb.edu/microbook/ch057.htm,
