Know Your Enemy

1. Know Your Enemy MSV • The maize streak virus (MSV) is an insect-transmitted virus that is endemic in sub-Saharan Africa. • It is transmitted by an African leafhopper. • It can in certain years devastate between 5% and 100% of a farmer's maize crop. • The development of resistant genetically modified maize varieties is currently under development in Africa.

2. עמידות הנגיף MSV • Maize streak monogeminivirus. • נגיפי דנ"א קטנים מאד. • חד-גדילי, קווי. • Total genome size 2.69 kb. • העברה: • Transmitted by a vector. • מועבר על ידי חרק.

3. Vector • Vector is an organism that does not cause disease by itself, but which spreads the infection by conveying pathogens from one host to another. • There are two types of vectors: • Mechanical vectors: the virus does not multiply within mechanical vectors. Mechanical vectors only physically transport viruses from host to host. • Biological vectors: the viruses must multiply within a biological vector before the biological vector can transmit the viruses.

4. Types of transmission • There are four basic types of transmission: • Non-persistent Transmission • These viruses are acquired from infected host plants through the probing behavior of the insect in very short periods of time. The insect then transmits the virus by probing on a healthy plant (5-30 seconds). Because the insect remains viruliferous (carrying or containing a virus ) for only short periods of time, it must probe on infected plants to re-acquire the virus. • Semi-persistent Transmission • Viruses are acquired and transmitted by feeding rather than by probing. The longer the insect feeds, the greater the rate of transmission. The virus is retained for a few days and varies with the virus/vector combination. There is no latent period — once the virus is acquired, it can be transmitted immediately.

5. Types of transmission • Circulative Non-propagative Transmission • Viruses transmitted in this manner are also acquired and transmitted by the feeding rather than the probing behavior of the insect vector. There is an 8- to 12-hour latent period for the virus to get from the gut to the salivary glands, and longer feeding periods increase the chances of acquisition. Once the insect has acquired the virus, it can remain viruliferous for the remainder of its life. The insect is capable of transmitting the virus to numerous plants within its lifetime. • Circulative Propagative Transmission • These viruses are acquired and transmitted by feeding as well, but can also be acquired by transovarial transmission (passage from parent to progeny through the egg). These viruses replicate in both the plant and the insect and often have deleterious effects on both types of hosts.

6. העברת הנגיף MSV - Transmitted by a vector • Transmitted in a persistent manner. • העברה מתמדת. • Virus does not multiply in the vector. • הנגיף אינו מתרבה בתוך החרק. • Not transmitted congenitally to the progeny of the vector. • אין העברה מולדת לצאצאי החרק.

7. עמידות הנגיף MSV - Transmitted by a vector • Not transmitted by mechanical inoculation. • אין העברה תוך כדי הרכבה. • Not transmitted by contact between plants. • Not transmitted by seed; not transmitted by pollen. • לא מועבר על ידי זרעים; לא על ידי אבקה.

8. Know Your Enemy MSV • In southern and central Africa, MSV is transmitted chiefly by Cicadulina mbila

9. MSV Latent Period • MSV undergoes a latent period in the vector before transmission can occur. • The length of this period is temperature dependent. • At 30øC, the minimum latent period is 6 - 12 hours, the medium period being 16 - 20 hours. • At 16øC, the minimum latent period is 85 hours. • The latent period represents the time required for the virus to pass from the insect's gut lumen tothe salivary glands, where it becomes available for inoculation.

10. Epidemiology MSV • Disease avoidance can be practiced by adjusting planting dates to avoid migrating leafhoppers landing on young plants. • The vector can be controlled by applying systemic insecticides to the planting furrow during maize planting.

11. מניעה MSV • However, the development and use of streak-resistant cultivars is probably the most effective and economically viable means of preventing streak epidemics. • Naturally occurring resistance to MSV has been found in maize on Reunion Island (where MSV has long been endemic). The resistance appeared to be simply inherited and was rapidly fixed in breeding, being easily transferred to other maize lines.

12. מניעה MSV • The incorporated resistance resulted in lowered disease incidence and reduced disease severity. • More recently, it has been shown that resistance to MSV in maize is quantitatively inherited, with relatively small numbers of genes involved. • Thus, it is envisaged that simple recurrent selection or modified back-cross breeding methods could be used to breed for MSV resistance in Africa.

14. הנגיף - • קדחת הנילוס המערבי נגרמת על ידי – West Nile VirusWNV, שהינו חלק ממשפחת ה-Flaviviruses. • הנגיפים תוקפים חולייתנים מסוגים שונים, כולל ציפורים ויונקים. • רוב הנגיפים מזן זה מועברים על ידי וקטורים - בעיקר יתושים וקרציונים. • Flaviviruses: share a common size (40-60nm), symmetry (enveloped, icosahedral nucleocapsid), nucleic acid (positive-sense, single stranded RNA approximately 10,000-11,000 bases), and appearance in the electron microscope

15. מחלת קדחת הנילוס המערבי • המחלה נקראת קדחת הנילוס המערבי, כיוון שהנגיף הגורם לה בודד לראשונה בשנת 1937 בתרבית מאישה ממחוז הנילוס המערבי שבאוגנדה. • קדחת הנילוס המערבי נגרמת ע"י נגיף המצוי בעופות ומועבר לאדם בעיקר על ידי יתושי הקולקס (culex). אין אפשרות של הדבקות אדם מאדם נגוע בנגיף, ולכן אין סכנה במגע עם אדם חולה. • המחלה מוכרת בארץ ובעולם כמחלה קלה (עליית חום קלה, כאבי ראש וכאבים בגוף,פריחה קלה בעור והתנפחות בלוטות הלימפה) עם אפשרות לסיבוכים. הנגיף עשוי לגרום לדלקת מוח (encephalitis) או דלקת קרום המוח (meningitis) • בשנת 2000 הייתה התפרצות של המחלה בבני אדם שהתבטאה בעלייה במספר החולים הקשים שחלקם הסתיימו במוות.

16. מהם קבוצות הסיכון להידבקות במחלת קדחת הנילוס המערבי ? קבוצות הסיכון הם אנשים בעלי מערכת חיסון לא תקינה - קשישים וחולים במחלות כרוניות. טיפול - אין למחלה זו טיפול ספציפי. במקרים קשים יש צורך בטיפול סיעודי (מתן נוזלים, הזנה, תמיכה נשימתית במקרה הצורך) כדי לשמור על יציבות מצבו הרפואי של החולה ולמנוע הדרדרות. עדיין אין חיסון או תרופה לנגיף, אם כי צוותים עובדים על פיתוח חיסון.

17. יתושים והעברת המחלה • נקבת היתוש מטילה את הביצים במים. הזחלים והגלמים חיים במים עומדים או זורמים לאט. • היתושים הבוגרים חיים מחוץ למים בעיקר סביב צמחיה ושיחים. • הם פעילים בעיקר בשעות החשיכה, וניזונים מסוכרים שבצמחים. רק הנקבה מוצצת דם (עוקצת) לצורך התפתחות הביצים.

18. יתושים והעברת המחלה • תוך כדי מציצת הדם היתושה עלולה להעביר את נגיף קדחת הנילוס המערבי מבעלי חיים (בעיקר בעלי כנף) לאדם. • מניעה של מפגעי יתושים היא הדרך היעילה ביותר למנוע את העברת מחלת קדחת הנילוס המערבי לבני אדם.

22. מניעת התפתחות יתושים על מנת למנוע התפתחות יתושים יש לאתר ולטפל בכל מקור מים עומדים בבית ובסביבתו

23. מניעת התפתחות יתושים • · מערכת הביוב - לתקן לאטום ולמנוע דליפות. • · גגות ומקלטים - ליבש ולנקז. • · דליים, צמיגים, חביות ומכלים אחרים - לרוקן. • · בריכות נוי - להכניס דגי גמבוזיה.

24. התגוננות מפני עקיצות יתושים (בשעות הערב והלילה) • 1 . מניעת כניסת יתושים לתוך הבתים באמצעות התקנת רשתות על פתחי הבית. • 2 . קטילת יתושים באמצעות ריסוס חלל החדר או משטחים עליהם נחים היתושים בתכשירים להדברת יתושים או חרקים מעופפים שאושרו על ידי המשרד לאיכות הסביבה.

25. התגוננות מפני עקיצות יתושים (בשעות הערב והלילה) • 3 . דחיית יתושים: בתוך הבית באמצעות תכשירי אידוי (טבליות או נוזל), מחוץ לבית באמצעות סלילים או נרות. יש להשתמש בתכשירים שאושרו על ידי המשרד לאיכות הסביבה .

26. התגוננות מפני עקיצות יתושים (בשעות הערב והלילה) • 4 . מניעת עקיצות באמצעות תכשירים המיועדים למריחה על הגוף. תכשירים אלה מאושרים על ידי משרד הבריאות.

27. Patterns of infection A delicate balance • Natural infections can be rapid and self-limiting (acute infections) or • Long-term (persistent infections) • Variations and combinations of these two modes abound • We can already provide detailed descriptions • However, we are in the early days of understanding the molecular mechanisms required to initiate or maintain any specific one.

28. Mechanisms of Survival of Viruses in Nature • Transmissibility: related to virion release from the patient and quantity • Seasonality: affects the survival of viruses • Community size: determines if acute or persistence infections are perpetuated • Effects of immunity types • Antigenic drift, shift and reassortment

29. Mechanisms of Survival of Viruses in NaturePersistent Infections •  Herpesviridae, • Adenoviridae, • Papovaviridae, • Hepadnaviridae, • Arenaviridae, Togaviridae, • Flaviviridae, • Retroviridae.

30. Mechanisms of Survival of Viruses in NaturePersistent Infections • Arenaviruses, • Herpesviruses, • Retroviruses • and some Togaviruses

31. Tropism • viruses are not compatible with the biochemistry of all types of cells. • The type of cell within a given individual host cell, which a virus can infect, is referred to as a virus' tropism. • Tropism is a predilection of viruses to infect certain tissues and not others. • An enterotropic virus replicates in the gut. • A neurotropic virus replicates in the nerves. • Some viruses are pantropic. • HSV is often said to be neurotropic but in fact it is pantropic. • Different species of viruses tend to vary both in their specific tropisms as well as in the breadth of their tropisms (i.e., they differ both in what cells they can infect and in how many different kinds of cells they can infect).

32. Tropism • an inability of the virus to successfully adsorb and/or enter cells because of an incompatibility between virus capsid proteins (or virus envelope proteins ) and the host receptor molecule • an incompatibility between the biochemistry of the virus and the biochemistry of the host. • some viruses infect one or only a few species while others (such as the rabies virus or poxviruses) are capable of infecting a broad range of species. • Change in tropism can occur through virus mutation.

33. Tropism • Example: distemper on the Serengeti: • "Between 1993 and 1994, a CDV epidemic swept through villages to the west of the Serengeti, killing thousands of domestic dogs. Monoclonal antibody tests show similarities between this strain and the one that infected the lions. The researchers propose that the virus then entered the park, perhaps via jackals and spotted hyenas, which frequently scavenge near humans. Because CDV is shed in mucus, these animals, in turn, probably infected lions at kill sites, where there is often a lot of biting and snarling between species. . . at least 1000 of the park's 3000 lions are thought to have died of the disease." Other variants of CDV-like viruses have also been identified which infect dolphins, horses, and seals.” (p. 596, Morell, 1996)

34. Evasion of immune defense Many viruses have evolved active mechanisms for bypassing or disarming host defenses. For example,…

35. Many viruses have evolved active mechanisms for bypassing or disarming host defenses. For example,… Apoptosis (programmed cell death) Apoptosis is a process of deliberate “suicide” by a cell in a multicellular organism. It is one of the main types of programmed cell death , and involves a series of biochemical events that lead to the death of the cell. The apoptotic process is needed to dispose of cell corpses and fragments, for proper development and the destruction of cells that represent a threat to the integrity of the organism … some viruses express proteins that block the apoptotic process that should activated in virus-infected cells.

36. Many viruses have evolved active mechanisms for bypassing or disarming host defenses. For example,… Antigenic variation • Antigenic drift is the appearance of virus with a slightly altered surface protein (antigen) structure • Antigenic shift is a major change in the surface protein. This process occurs when viruses with segmented genomes exchange genomes after coinfection.

37. Influenza virus provides the classic paradigm of antigenic drift and shift. Antigenic shift, not drift, was the driving force for the five pandemics of human influenza during the XIX-XX centuries

38. General patterns of infection עומס הנגיפי כנגד ציר הזמן • Acute הנגיף הושמד תוך 7-10 ימים • Persistent התסמינים יכולים להופיע (או לא!) ממש לקראת המוות • Latent • Slow

39. General patterns of infection • The time when symptoms appear is indicated by the red shaded area, and the period in which infectious virus is released is indicated by the bracket.

40. Acute infection • An acute infection is an infection that develops rapidly and only lasts a short time, rapid production of virus followed by rapid resolution (SARS, influenza virus and rhinovirus).

41. Acute infections present common public health problems • The nature of an acute infection presents difficult problems for physicians, epidemiologists, and others. • The main problem is that by the time people feel ill most acute infections are essentially complete and the virus has spread to the next host.

42. Multiple Acute infections in a Single Host • Model of varicell-zoster virus infection and spread.

43. Pathogenic Effects of an Acute Infection • Many symptoms of an a.i. are actually due to a host immune response. • Nevertheless, an acute viral infection can cause considerable damage because infected cells are killed either by infection or by the immune system. • If a sufficient number of cells are infected, severe problems may result.

44. Persistent Infections • Infectious virus may be produced continuously or intermittently for months or years. • virus is not cleared but remains in specific cells of infected individuals. • Persistent infections may involve stages of both silent and productive infection without rapidly killing or even producing excessive damage of the host cells. • Reactivation of a latent infection may be triggered by various stimuli, including changes in cell physiology, superinfection by another virus, and physical stress or trauma.

45. Persistent Infections • No measures to eradicate persistent viruses have been developed. Vaccination and antiviral drugs can reduce the frequency of clinical recurrence and symptoms, yet the virus continues to remain associated with the host. • Distinctions have been made between p.i. (chronic infections) and latent/slow infections. • Many viruses can establish a persistent infection.

46. Persistent Infections

47. Direct Infection of the Immune System Itself

48. An Example of a Virus that Causes Persistent Infections • Measles Virus provides a provocative example of the delicate balance. • Many important questions remain unanswered about how this human pathogen switches from an acute to a persistent infection. • It does so despite an active immune response.

49. Measles Measles is one of the most contagious human viruses, with about 40 million infections occurring worldwide each year, resulting in 1 to 2 million deaths.

50. Latent Infections • Latent infections can be characterized by four general properties: • The cell cycle is interrupted • Immune detection of the harboring cell is reduced or eliminated • Expression of productive cycle viral genes is absent or inefficient • The viral genome persists intact