Virus Tissue Tropism

1. Virus Tissue Tropism • Targeting of the virus to specific tissue and cell types • Receptor Recognition • CD4+ cells infected by HIV • CD155 acts as the receptor for poliovirus

2. DNA Viruses • Herpesviridae • Poxviridae

3. Herpesviridae • Causes diseases in animals • The family name is derived from the Greek word herpein ("to creep"), referring to the latent, recurring infections typical of this group of viruses. (Can cause lytic or latent infections)

4. Causes diseases in animals • The family name is derived from the Greek word herpein ("to creep"), referring to the latent, recurring infections typical of this group of viruses. (Can cause lytic or latent infections)

5. More than 90% of adults have been infected with at least one of these, and a latent form of the virus remains in most people.

6. All herpesviruses are enveloped viruses composed of relatively large double-stranded, linear DNA encoding 100-200 genes encased within an icosahedral capsid.

7. Poxviridae • Causes diseases in vertebrates and invertebrates

8. Causes diseases in vertebrates and invertebrates • Five species of Herpesviridae – • HSV-1 and HSV-2 (both of which can cause orolabial herpes and genital herpes), • Varicella zoster virus (which causes chicken-pox and shingles), • Epstein-Barr virus (which causes mononucleosis) • Cytomegalovirus

9. Smallpox • Variola is a large brick-shaped virus measuring approximately 302 to 350 nm by 244 to 270 nm, with a single linear ds DNA of 186 (kbp) in size.

10. The life cycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. • Poxviruses are unique among DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus.

11. In order to replicate, poxviruses produce a variety of specialized proteins not produced by other DNA viruses, the most important of which is a viral-associated DNA-dependent RNA polymerase.

12. Smallpox in the New World • In the early 16th century smallpox began to imported into the western hemisphere. • The Spanish inadvertently owe success in conquering the Aztec and Incas in Mexico to smallpox. • Smallpox arrived in North America via Canada, and Mexico.

13. The disease killed an estimated 400,000 Europeans annually during the closing years of the 18th century (including five reigning monarchs), and was responsible for a third of all blindness.

14. Of all those infected, 20–60%—and over 80% of infected children—died from the disease.Smallpox was responsible for an estimated 300–500 million deaths during the 20th century. • As recently as 1967, the WHO estimated that 15 million people contracted the disease and that two million died in that year.

15. Smallpox as Biological Warfare • Lord Jeffrey Amherst, Commanding General of British Forces in North America during the French and Indian War. (1754-1763) • Used blankets (smallpox blankets) coated with smallpox dust as germ warfare to wipe out the Native American population.

17. RNA viruses • Poliovirus • Rhinovirus • Norovirus • Influenza • Rotavirus • Hantavirus • Ebola

18. RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense, or ambisense RNA viruses.

19. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell • Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation.

20. Purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle • Purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA; each virion can be transcribed to several positive-sense RNAs.

21. Ambisense RNA viruses resemble negative-sense RNA viruses, except they also translate genes from the positive strand.

22. Poliovirus Properties of the virus • Enterovirus. • + stranded RNA virus • Transmitted by the faecal oral route. • Cause of gastrointestinal illness and poliomyelitis.

23. Poliovirus

24. Virus Infection Viremia Gut Neuronal tissues Virus excretion in the feces Paralysis Poliovirus Infection Non-neuronal tissues

25. A B 40 30 20 Number of cases (in thousands) 10 0 1950 1960 1970 1980 Incidence of Poliomyelitis Poliovirus vaccines A: Salk – killed inactivated vaccine. B: Sabin – live attenuated vaccine

26. Influenza A virus Properties of the virus • Myxovirus • Enveloped RNA virus • Infects a wide range of animals other than humans • Undergoes extensive antigenic variation • Major cause of respiratory infections

27. 600 500 400 300 200 100 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Weekly consultation rates for influenza and influenza-like illness: Weekly Returns Service of the Royal College of General Practitioners, 1988 to 1999 Epidemic activity Higher than expected seasonal activity Baseline activity Rate per 100 000 population Normal seasonal activity Year CDR Weekly Report: 5th November 1999

28. Norovirus • Genus of genetically diverse single-stranded RNA, non-enveloped viruses in the Caliciviridae family • The known viruses in the genus are all considered to be the variant strains of a single species called Norwalk virus.

29. Norovirus • The viruses are transmitted by fecally contaminated food or water, by person-to-person contact, and via aerosolization of the virus and contamination of surfaces. • Noroviruses are the most common cause of viral gastroenteritis in humans, and affect people of all ages.

30. Rotovirus • Genus of dsRNA virus in the family Reoviridae. • 11 unique double helix molecules of RNA which are 18,555 nucleotides in total. Each helix codes for a protein. • The RNA is surrounded by a three-layered icosahedral protein capsid. Viral particles are up to 76.5 nm in diameter and are not enveloped.

31. Rotovirus • Nearly every child in the world has been infected with rotavirus at least once by the age of five. • There are five species of this virus, referred to as A, B, C, D, and E. Rotavirus A, the most common species, causes more than 90% of rotavirus infections in humans.

32. Rotovirus • Transmitted by the fecal-oral route. It infects and damages the cells that line the small intestine and causes gastroenteritis.

33. HIV • HIV is a member of the genus Lentivirus part of the family Retroviridae. • ss positive-sense, enveloped virus • HIV is different in structure from other retroviruses. It is roughly spherical[ with a diameter of about 120 nm, around 60 times smaller than a RBC yet large for a virus.

34. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. • Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells.

35. HIV infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells.

36. Ebola • Ebolavirions are filamentous particles of ssRNA that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched.

37. The current outbreak in west Africa, (first cases notified in March 2014), is the largest and most complex Ebola outbreak since the Ebola virus was first discovered in 1976. There have been more cases and deaths in this outbreak than all others combined. • As of Oct 8, 2014: • Total Cases: 8400 • Laboratory-Confirmed Cases: 4656 • Total Deaths: 4033

39. Ebola • Cells lining the inside of blood vessels (endothelial cells), macrophages, monocytes and liver cells are the main targets of infection. • After infection, a secreted glycoprotein, known as small soluble glycoprotein (sGP) or as the Ebola virus glycoprotein (GP), is synthesized

40. Human-to-human transmission occurs only via direct contact with blood or body fluid from an infected person (including embalming of an infected dead body), or by contact with objects contaminated by the virus, particularly needles and syringes.

41. Other body fluids that may transmit ebolaviruses include saliva, mucus, vomit, feces, sweat, tears, breast milk, urine, and semen. • The dried virus can live on doorknobs and countertops for several hours • Entry points include the nose, mouth, eyes, or open wounds, cuts and abrasions

42. Humans are not infectious until they develop symptoms. • Symptoms usually begin suddenly with an influenza-like stage characterized by fatigue, fever, headaches, and pain in the joints, muscles, and abdomen. • Vomiting, diarrhea, and loss of appetite are also common.

43. Less common symptoms include sore throat, chest pain, hiccups, shortness of breath, and trouble swallowing. • The average time between contracting the infection and the start of symptoms (incubation period) is 8 to 10 days, but it can vary between 2 and 21 days

44. In the bleeding phase, which typically begins five to seven days after first symptoms,internal and subcutaneous bleeding may present itself in the form of reddened eyes and bloody vomit and/or stools.

45. People remain infectious as long as their blood and body fluids, including semen and breast milk, contain the virus. Men who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness

46. The disease is only spread by direct contact with the secretions from someone who is showing signs of infection • A person's ability to spread the disease is often limited as the individual is often too sick to travel during the infectious stages of the disease.

47. As transmission via air is generally ruled out, the possibility of transmission between non-seat-mate airline passengers is generally ruled out

48. What about pets? • In the 2001-2002 outbreak in Gabon, scientists found signs of the virus in 25% of the dogs living near the outbreak. The animals were not symptomatic, nor did they die during the time the scientists were studying them.

49. Pets? • So..the animals came in contact with Ebola virus and their immune systems responded. • Whether or not dogs shed Ebola once their immune systems encounter it remains to be seen. • Scientists are studying the pets of the infected humans currently. • Cats have not found to contract virus.

50. At this time, there have been no reports of dogs or cats becoming sick with Ebola or of being able to spread Ebola to people or other animals. • Even in areas in Africa where Ebola is present, there have been no reports of dogs and cats becoming sick with Ebola.