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ZIKA VIRUS – A CONCERN
FOR MALE FERTILITY
Chetana rai
Msc. Clinical Microbiology
INTRODUCTION
o Zika virus is a mosquitoes-borne flavivirus belong to
the family Flaviviridae, that was first identified in
Uganda in 1947 in monkey.
o It was later identified in human in 1952.
o ZIKV is primarily transmitted to human through bite of
an infected mosquito from Aedes genus mainly Aedes
aegypti.
o The virus was named after the region where it was
found in the Zika Forest of Uganda.
.
.
HISTORY
 1947 : Routine surveillance for Yellow fever in the Zika
forest of Uganda, ZIKV was isolated in sample taken
from the capitive sentinel rhesus monkey.
 1954 : The virus is isolated from a girl in Eastern
Nigeria.
 1964 : A researcher in Uganda who fell ill while working
with Zika strains isolated from mosquitoes provides the
first proof, by virus isolation and re-isolation, that Zika
virus causes human disease.
 1969-1983 : Geographical distribution of Zika expands
to equatorial Asia (India, Malaysia, Indonesia, and
Pakistan),where the virus is detected in mosquito.
HISTORY CONT.…
 2007 : First large out break in humans on the pacific
island of Yap. An estimated 73% of Yap residents over
3years of age were infected with Zika virus.
o 2013-2014 : Outbreaks in 4 other groups of Pacific
island: French Polynesia, Easter island, the cook islands
and New Caledonia.
o Outbreak in French Polynesia, is intensively
investigated. The results are reported to WHO on
November 2015 and January 2016.
o These reports indicates a possible association between
Zika virus infection and cogenital malformations and
severe neurological and autoimmune complications.
o In Feb 2015,Brazil detect cases of fever and rashes that
were confirmed to be Zika virus in May 2015.
SYMPTOMS
Incubation period in man is about 3-12 days after bite
of an infected mosquito.
 Headache
 Fever
 Skin rashes (exanthema)
 Pink eye
 Conjunctivitis
 Muscle and joint pain
 Malaise
These symptoms are mild and usually last for 2-7
days.
TRANSMISSION
1. Through mosquito bites.
2. Rarely from mother to child.
3. Through sexual contact.
4. Through blood transfusion.
.
 Previously it was thought that the virus, which is
passed on through mosquito bites, was only
dangerous for pregnant women, because it can
lead to babies being born with shrunken heads and
brain damage, a condition known as microcephaly.
In rare cases it can also lead to Guillain-Barre
syndrome which can cause paralysis and lead to
death.
.
.
CONSEQUENCES
 Most of the research to understand the
consequences of Zika virus infection has focused on
how the virus affects pregnant women and causes
severe birth defects in their developing fetuses.
 But a new study in mice suggests that Zika infection
also may have worrisome consequences for men
that interfere with their ability to have children.
EFFECTS
Zika virus has the potential to cause serious health
problems, including severe birth defects in humans.
There are a few things that are already
known about Zika virus and men. One is that the virus
can be sexually transmitted. Another is Zika has been
detected in the semen of men months after they were
infected.
But the damaging effects of Zika might not end
there: results of a new mouse study show that the
virus may also have an unexpected negative—and
possibly long-lasting—impact on male fertility.
RECENT STUDY
 In a new mouse study, a team of investigators led
by Kelle Moley and Michael Diamond has shown
that ZIKV persists in the testes, sperm and
epididymis of mice 21 days after infection and that
persistence of the virus is associated with testicular
damage, oligospermia and severely impaired male
fertility.
 The team infected wild-type C57BL/6 mice with
mouse-adapted African ZIKV (strain Dakar 41519)
or the closely related Dengue virus (DENV) (strain
D2S20).
 To facilitate infection and dissemination of the
viruses, mice were also administered a single dose
of a blocking monoclonal antibody that suppressed
IFN α/β receptor 1 signalling.
.
o Within 7 days of infection, viral RNA and infectious
particles were detected in all tissues of the male
reproductive tract of mice infected with ZIKV but not in
those infected with DENV.
o By day 14, the blood–testis barrier was breached and
the virus was detected throughout the testes in ZIKV-
infected mice. Marked infiltration of CD45+ cells and
testicular cell death were also noted.
o Persistence of the virus at day 21 was accompanied
by progressive destruction of the testes (noticeably
reduced size and weight), reduced production of
testosterone and inhibin-β, and decreased sperm
counts (both total and motile). Crucially, fecundity was
lower in female mice mated with ZIKV-infected male
mice than in female mice mated with uninfected
controls.
CAPTION: IMMUNOFLUORESCENCE STAINING SHOWING THAT THE TESTES OF ZIKA-FREE MICE (LEFT) ARE FULL OF
DEVELOPING SPERM (PINK), WHILE THE TESTES OF ZIKA-INFECTED MICE (RIGHT) CONTAIN VERY FEW SPERM.
RESULT OF THIS STUDY
 By using a mouse-adapted African ZIKV strain (Dakar
41519), they evaluated the consequences of infection
in the male reproductive tract of mice. They observed
persistence of ZIKV, but not the closely related
dengue virus (DENV), in the testis and epididymis of
male mice, and this was associated with tissue injury
that caused diminished testosterone and inhibin B
levels and oligospermia. ZIKV preferentially infected
spermatogonia, primary spermatocytes and Sertoli
cells in the testis, resulting in cell death and
destruction of the seminiferous tubules.
HOW IT EFFECTS MALE FERTILITY
 ZIKV is found mainly in Sertoli cells, mitotic cells,
and midmeiotic germ cells in the testis, the viral
load in epididymal spermatozoa is already
substantial 7 days after infection. This observation
provides a clear indication that ZIKV can infect
spermatozoa directly and efficiently in the
epididymal lumen.
 ZIKV preferentially infected spermatogonia,
primary spermatocytes and Sertoli cells in the
testis, resulting in cell death and destruction of the
seminiferous tubules
.
 The testicular interstitial cells consisting mostly of the
steroidogenic Leydig cells and leukocytes — are
virus-free up to day 21 post infection, but Sertoli cells
seem to be particularly susceptible to ZIKV infection.
Although the Sertoli cells are fairly robust, impairment
of their function can quickly accelerate and magnify
the extent of spermatogenic damage, as each Sertoli
cell sustains dozens of germ cells at different stages
of their development.
CONCLUSION
 All previously researches are made to understand the
consequences of Zika virus infection on pregnant
women and its causes severe birth defects in their
developing fetuses.
 But Recent research has shown that the mosquito-
borne Zika virus has the potential to cause impact on
male fertility.
 This study on mice suggest that men might face low
testosterone levels and low sperm count after Zika
infection which affect their fertility.
.
‘The more we learn about
the Zika virus, the more
interesting and alarming it
becomes’’.
REFERENCES
 http://dx.doi.org/10.1038/nature20556 (2016)
 http://www.nature.com/nrendo/journal/v13/n1/full/nr
endo.2016.191.html
 https://directorsblog.nih.gov/2016/11/08/could-zika-
virus-have-lasting-impact-on-male-fertility/
 https://www.niaid.nih.gov/diseases-conditions/zika-
virus
 http://www.telegraph.co.uk/science/2016/10/31/zika
-virus-could-cause-infertility-in-men-new-study-
suggests/
 http://www.nature.com/nature/journal/v540/n7633/fu
ll/nature20556.htm

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Zika virus – a concern for male fertility

  • 1. ZIKA VIRUS – A CONCERN FOR MALE FERTILITY Chetana rai Msc. Clinical Microbiology
  • 2. INTRODUCTION o Zika virus is a mosquitoes-borne flavivirus belong to the family Flaviviridae, that was first identified in Uganda in 1947 in monkey. o It was later identified in human in 1952. o ZIKV is primarily transmitted to human through bite of an infected mosquito from Aedes genus mainly Aedes aegypti. o The virus was named after the region where it was found in the Zika Forest of Uganda.
  • 3. .
  • 4. .
  • 5. HISTORY  1947 : Routine surveillance for Yellow fever in the Zika forest of Uganda, ZIKV was isolated in sample taken from the capitive sentinel rhesus monkey.  1954 : The virus is isolated from a girl in Eastern Nigeria.  1964 : A researcher in Uganda who fell ill while working with Zika strains isolated from mosquitoes provides the first proof, by virus isolation and re-isolation, that Zika virus causes human disease.  1969-1983 : Geographical distribution of Zika expands to equatorial Asia (India, Malaysia, Indonesia, and Pakistan),where the virus is detected in mosquito.
  • 6. HISTORY CONT.…  2007 : First large out break in humans on the pacific island of Yap. An estimated 73% of Yap residents over 3years of age were infected with Zika virus. o 2013-2014 : Outbreaks in 4 other groups of Pacific island: French Polynesia, Easter island, the cook islands and New Caledonia. o Outbreak in French Polynesia, is intensively investigated. The results are reported to WHO on November 2015 and January 2016. o These reports indicates a possible association between Zika virus infection and cogenital malformations and severe neurological and autoimmune complications. o In Feb 2015,Brazil detect cases of fever and rashes that were confirmed to be Zika virus in May 2015.
  • 7. SYMPTOMS Incubation period in man is about 3-12 days after bite of an infected mosquito.  Headache  Fever  Skin rashes (exanthema)  Pink eye  Conjunctivitis  Muscle and joint pain  Malaise These symptoms are mild and usually last for 2-7 days.
  • 8. TRANSMISSION 1. Through mosquito bites. 2. Rarely from mother to child. 3. Through sexual contact. 4. Through blood transfusion.
  • 9. .  Previously it was thought that the virus, which is passed on through mosquito bites, was only dangerous for pregnant women, because it can lead to babies being born with shrunken heads and brain damage, a condition known as microcephaly. In rare cases it can also lead to Guillain-Barre syndrome which can cause paralysis and lead to death.
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  • 12. CONSEQUENCES  Most of the research to understand the consequences of Zika virus infection has focused on how the virus affects pregnant women and causes severe birth defects in their developing fetuses.  But a new study in mice suggests that Zika infection also may have worrisome consequences for men that interfere with their ability to have children.
  • 13. EFFECTS Zika virus has the potential to cause serious health problems, including severe birth defects in humans. There are a few things that are already known about Zika virus and men. One is that the virus can be sexually transmitted. Another is Zika has been detected in the semen of men months after they were infected. But the damaging effects of Zika might not end there: results of a new mouse study show that the virus may also have an unexpected negative—and possibly long-lasting—impact on male fertility.
  • 14. RECENT STUDY  In a new mouse study, a team of investigators led by Kelle Moley and Michael Diamond has shown that ZIKV persists in the testes, sperm and epididymis of mice 21 days after infection and that persistence of the virus is associated with testicular damage, oligospermia and severely impaired male fertility.  The team infected wild-type C57BL/6 mice with mouse-adapted African ZIKV (strain Dakar 41519) or the closely related Dengue virus (DENV) (strain D2S20).  To facilitate infection and dissemination of the viruses, mice were also administered a single dose of a blocking monoclonal antibody that suppressed IFN α/β receptor 1 signalling.
  • 15. . o Within 7 days of infection, viral RNA and infectious particles were detected in all tissues of the male reproductive tract of mice infected with ZIKV but not in those infected with DENV. o By day 14, the blood–testis barrier was breached and the virus was detected throughout the testes in ZIKV- infected mice. Marked infiltration of CD45+ cells and testicular cell death were also noted. o Persistence of the virus at day 21 was accompanied by progressive destruction of the testes (noticeably reduced size and weight), reduced production of testosterone and inhibin-β, and decreased sperm counts (both total and motile). Crucially, fecundity was lower in female mice mated with ZIKV-infected male mice than in female mice mated with uninfected controls.
  • 16. CAPTION: IMMUNOFLUORESCENCE STAINING SHOWING THAT THE TESTES OF ZIKA-FREE MICE (LEFT) ARE FULL OF DEVELOPING SPERM (PINK), WHILE THE TESTES OF ZIKA-INFECTED MICE (RIGHT) CONTAIN VERY FEW SPERM.
  • 17. RESULT OF THIS STUDY  By using a mouse-adapted African ZIKV strain (Dakar 41519), they evaluated the consequences of infection in the male reproductive tract of mice. They observed persistence of ZIKV, but not the closely related dengue virus (DENV), in the testis and epididymis of male mice, and this was associated with tissue injury that caused diminished testosterone and inhibin B levels and oligospermia. ZIKV preferentially infected spermatogonia, primary spermatocytes and Sertoli cells in the testis, resulting in cell death and destruction of the seminiferous tubules.
  • 18. HOW IT EFFECTS MALE FERTILITY  ZIKV is found mainly in Sertoli cells, mitotic cells, and midmeiotic germ cells in the testis, the viral load in epididymal spermatozoa is already substantial 7 days after infection. This observation provides a clear indication that ZIKV can infect spermatozoa directly and efficiently in the epididymal lumen.  ZIKV preferentially infected spermatogonia, primary spermatocytes and Sertoli cells in the testis, resulting in cell death and destruction of the seminiferous tubules
  • 19. .  The testicular interstitial cells consisting mostly of the steroidogenic Leydig cells and leukocytes — are virus-free up to day 21 post infection, but Sertoli cells seem to be particularly susceptible to ZIKV infection. Although the Sertoli cells are fairly robust, impairment of their function can quickly accelerate and magnify the extent of spermatogenic damage, as each Sertoli cell sustains dozens of germ cells at different stages of their development.
  • 20. CONCLUSION  All previously researches are made to understand the consequences of Zika virus infection on pregnant women and its causes severe birth defects in their developing fetuses.  But Recent research has shown that the mosquito- borne Zika virus has the potential to cause impact on male fertility.  This study on mice suggest that men might face low testosterone levels and low sperm count after Zika infection which affect their fertility.
  • 21. . ‘The more we learn about the Zika virus, the more interesting and alarming it becomes’’.
  • 22. REFERENCES  http://dx.doi.org/10.1038/nature20556 (2016)  http://www.nature.com/nrendo/journal/v13/n1/full/nr endo.2016.191.html  https://directorsblog.nih.gov/2016/11/08/could-zika- virus-have-lasting-impact-on-male-fertility/  https://www.niaid.nih.gov/diseases-conditions/zika- virus  http://www.telegraph.co.uk/science/2016/10/31/zika -virus-could-cause-infertility-in-men-new-study- suggests/  http://www.nature.com/nature/journal/v540/n7633/fu ll/nature20556.htm