Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms

Data on the evolution of natural SIV infection in chimpanzees (SIVcpz) and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (Pan troglodytes schweinfurthii), and no data exist for Central chimpanzees (Pan troglodytes troglodytes), the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a P.t.troglodytes chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection.

Results: A male chimpanzee (Cam155), 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine.

Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm3 in 2004 vs 287 in 2009), a severe thrombocytopenia (130,000 cells/mm3 in 2004 vs 5,000 cells/mm3 in 2009), a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg) and frequent periods of infections with diverse pathogens.DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpzPtt-Cam155 genomes. SIVcpzPtt-Cam155 was phylogenetically related to other SIVcpzPtt from Cameroon (SIVcpzPtt-Cam13) and Gabon (SIVcpzPtt-Gab1).

Ten molecular clones 5 years apart, spanning the V1V4 gp120 env region (1,100 bp), were obtained. Analyses of the env region showed positive selection (dN-dS>0), intra-host length variation and extensive amino acid diversity between clones, greater in 2009.

Over 5 years, N-glycosylation site frequency significantly increased (p<0.0001).

Conclusions: Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected P.t.troglodytes chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that SIVcpz can be pathogenic in its host, as previously described in P.t.schweinfurthii.

Although studying the impact of SIV infection in wild apes is difficult, efforts should be made to better characterize the pathogenicity of the ancestors of HIV-1 in their natural host and to find out whether SIV infection also plays a role in ape population decline.

Author: Lucie EtienneEric NerrienetMatthew LeBretonGodwin Tafon BibilaYacouba FoupouapouognigniDominique RoussetAhmadou NanaCyrille DjokoUbald TamoufeAvelin AghokengEitel Mpoudi-NgoleEric DelaporteMartine PeetersNathan WolfeAhidjo Ayouba

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Testing Hair From Asian Monkeys Living Close To People May Provide Early Warnings of Toxic Threats to Humans and Wildlife

Macaques living close to people share the same ecological niche and exposures

Testing hair from Asian monkeys living close to people may provide early warnings of toxic threats to humans and wildlife, according to a study published online this week in the American Journal of Physical Anthropology.

In parts of South and Southeast Asia, macaques and people are synanthropic, which means they share the same ecological niche. They drink from identical water sources, breathe the same air, share food sources, and play on the same ground.

"Macaques are similar to humans anatomically, physiologically and behaviorally," said the senior author on the study, Dr. Lisa Jones-Engel, a senior research scientist at the National Primate Research Center at the University of Washington in Seattle.

"They are also similar in their response to toxic exposures," said lead author Dr. Gregory Engel, a physician at Swedish Cherry Hill Family Medicine in Seattle and a research scientist at the UW National Primate Research Center. When macaques live in environments polluted by motor vehicles, openly disposed garbage, and industrial waste, they can come into contact with toxic substances such as lead, just as their human neighbors might.

Lead toxicity, the authors noted, remains a significant public health problem around the world. Intense exposure to lead can damage the nervous, circulatory, and reproductive systems, as well as the kidneys and liver. Exposure during childhood, according to other studies, may cause more subtle effects, such as decreased intelligence.

According to Jones-Engel, the researchers hypothesized that young macaques, in particular, would be good sentinels for human exposure to lead exposure.

"Young macaques share a propensity for curiosity and have a penchant for picking up objects and inserting them into their mouths, just as young children do," Jones-Engel noted. "A juvenile macaque has all the curiosity and energy of a toddler, and then some! Plus their parents aren't well informed about environmental hazards."

She and her team of primatologists, physicians, epidemiologists, veterinarians and toxicologists decided to test urban macaques as a potential early indicator that their human neighbors, especially the children, are being exposed to lead and other toxic metals. They took hair samples from three groups of free-ranging macaques at the Swoyambhu temple overlooking Kathmandu, Nepal. The macaques patrolling the site have abundant contact with people and with human-made environments. This World Heritage Site temple is located in a densely populated urban area with poor infrastructure that leaves point sources like discarded lead batteries, flaking leaded paint, and lead contaminated soil, a by-product of decades of leaded fuel, in the environment.

Hair lead levels differed among the three groups of macaques, and were much higher in younger macaques. The researchers' data did not support the idea that these lead levels were from basic differences in the animals' diet, and instead suggested that, in this population of macaques, behavioral or physiological factors among young macaques might play a significant role in determining exposure to lead and subsequent tissue concentration.

Animal sentinels of poisonous conditions for people have been used for a long time. From the 19th century and well into the 20th century coal miners sent canaries into mining shafts to check if the air was safe to breathe.

"While using animal sentinels is not a new phenomenon, we argue that not all animal species are relevant models for human toxicant exposures, but young macaques that share the same ecological niche with humans may be one of the best animal sentinels we have," Engel said.

Scientists testing for environmental exposures also don't want to hurt the animals they are monitoring. Collecting a few hairs is a gentle, non-invasive approach.

The researchers noted, "All of these factors contribute to making synanthropic macaques -- those that share the environment with humans -- potentially valuable as sentinels for toxic exposures and predictors of physiologic responses in humans."

The research team concluded, "Chemical analysis of hair is a promising, non-invasive technique for determining exposure to toxic elements in free-ranging, non-human primates, and further multidisciplinary research is needed to establish whether it can be used to predict lead levels in humans who live in the same areas."

In addition to Engel and Jones-Engel, other researchers on this study were Todd M. O'Hara and Tamara Cardona-Marek of the Institute of Arctic Biology at the University of Alaska, Fairbanks; John Heidrich of Quatros, LLC; Mukesh K. Chalise of the Central Department of Biology, Tribhuvan University; and Randall Kyes of the UW Department of Psychology and the UW National Primate Research Center.

The study was funded by grants from the Defense Advanced Research Projects Agency and the National Institutes of Health.

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At Least 45 Diseases Have Been Passed From Animals To Humans

REUTERS

Health workers culling poultry at Shoilpur village near the Indian city of Kolkata. The H5N1 bird flu pandemic spread across the world in 2003 causing widespread panic and has so far killed 260 people

The world is facing a growing threat from new diseases that are jumping the human-animal species barrier as a result of environmental disruption, global warming and the progressive urbanisation of the planet, scientists have warned.

At least 45 diseases that have passed from animals to humans have been reported to UN agencies in the last two decades, with the number expected to escalate in the coming years.

Dramatic changes to the environment are triggering major alterations to human disease patterns on a scale last seen during the industrial revolution. Montira Pongsiri, an environmental health scientist at the US Environmental Protection Agency in Washington, says that previous transitions in

human history have had a devastating impact in terms of the spread of disease.

"We appear to be undergoing a distinct change in global disease ecology. The recent emergence of infectious diseases appears to be driven by globalisation and ecological disruption," Dr Pongsiri said.

He and eight colleagues examined five emerging and re-emerging diseases – malaria, lyme disease (spread by ticks), Hantavirus (spread by mice and rats), West Nile disease (spread by mosquitoes), and schistosomiasis (spread by freshwater snails). They argue that changes in land use, farming practices and climate lie behind the increasing number of outbreaks.

The best known example of a disease that jumped the animal-human barrier and went on to cause a global pandemic is HIV, the virus that causes Aids. HIV is thought to have crossed from chimpanzees to humans in West Africa in the last century and more than 25 million people worldwide have since died from it.

The swine flu pandemic that emerged in Mexico last March also resulted from the mixing of viruses that infected pigs, birds and humans to create a new pandemic strain. Although it turned out to be milder than expected, future flu pandemics are expected in the coming decades that could have higher death rates and infect millions more people.

Dr Pongsiri and colleagues say that the number of people who succumbed to infectious diseases plummeted in the developed world during the industrial revolution, but the rise of manufacturing and pollution levels increased the incidence of chronic diseases including cancer, allergies and birth defects. Now, we are in the grip of another epidemiological transition driven by the destruction of plant and animal habitats, the loss of species and changes that have brought more humans into closer contact with animals than at any stage in human history, they say in the journal Bioscience.

David Murrell, lecturer in ecology at University College London, said: "Since 1940, over 300 new diseases have been identified, 60 per cent of which crossed to humans from animals and 70 per cent of these came from contact with wildlife. I would expect the emergence of new diseases from contact with animals to continue in this century."

A key factor has been increasing urbanisation, which has resulted in humans moving into previously untouched areas where they have come into closer contact with animals. At the same time, globalisation has meant newly emerged diseases have transmitted faster and more widely than in the past. "Before the world became so interconnected, deadly and newly emerged diseases were not capable of spreading widely," Dr Murrell said. "Now it is very possible that they will spread across countries and continents within days, thereby sustaining the outbreak.

"We don't know what's out there or how it might transmit. It is very difficult to predict. At least our government, with swine flu, is taking these things seriously now. The problem is if we deal with a threat successfully it leads to complacency. But these things are potentially serious. I would rather err on the side of caution."

Jan Slingenbergh, of the United Nations Food and Agriculture Organisation, said changes in animal farming have altered the circulation of viruses and bacteria including influenza capable of infecting humans. In countries like China, higher demand for poultry meat has led to a massive rise in populations of domestic wildfowl, he told the Emerging Health Threats Forum. In Southern China alone, there are now around 700 million domestic ducks.

In the case of flu, a growing number of viral subtypes have moved from wild animals into farmed and domestic waterfowl, which live in closer contact with humans. A similar expansion in the number of flu strains in pigs has also been seen over the past decade. "At the end of the 1990s, there was just one subtype of swine flu. Now there are three subtypes, each with multiple strains," Dr Slingenbergh added.

The behaviour of these new viruses is unpredictable – scientists don't know how likely they are to jump the species barrier into humans. But with more of them circulating, there is a higher chance of this happening, Dr Slingenbergh said. Flu viruses are getting closer to people and food, and agriculture practices are to blame.

He said: "There is no evidence to suggest this is going to end any time soon. Agriculture looks set to continue growing for another two decades, and we are only at the beginning of climate change."

Viral alert: Diseases that have spread from animals to humans

HIV

The emergence of HIV, the virus that causes Aids, is blamed on human incursion into the forests of West Africa, driven by pressure of population. Rising demand for food led to the growth of the bushmeat trade, and the slaughter of chimpanzees thought to be the animal reservoir for the HIV virus. People who ate chimpanzee meat, or whose blood got into cuts or wounds, were exposed to novel infectious agents providing the ideal breeding ground for the development of the new disease.

Aids is thought to have emerged during the latter half of the last century but was not identified in humans until young gay men began dying of a mysterious illness in San Francisco in the early 1980s. More than 25 million people have since succumbed to the disease.

The 30-year Aids pandemic is evidence of the catastrophic damage a virus can do when it jumps the species barrier from animals to humans. But HIV is not alone. There are many other viruses that have crossed the barrier or spread more widely as a result of changes in ecology and climate, causing death on a wide scale.

Hantavirus

In May 1993, a young, fit Native American in the South-west of the US developed a flu-like illness. He was rushed to hospital in New Mexico, but died very quickly. It was the first recognised case of Hantavirus pulmonary syndrome, a disease marked by high fever, chills and breathing problems, spread by mice and rats. In addition to the pulmonary illness, which kills four out of five people infected, hantaviruses also cause haemorrhagic fever, resulting in widespread internal bleeding. There is no treatment. One estimate suggests there are between 60,000 and 150,000 cases worldwide a year.

Any big increase in mouse numbers, as occurs with urbanisation, increases the risks. The 1993 outbreak in the US followed years of drought, which ended with heavy rainfall. The number of mice multiplied tenfold in a year, increasing the likelihood of their coming into contact with humans. A less severe form of the illness is endemic in northern Sweden, where there are around 4,500 cases a year.

Research has also shown that a proliferation of mouse species, many of which are immune to Hantavirus, lowers the risk of the disease. They compete with the hantavirus-infected mice, reducing their numbers and the risk of infection. Biodiversity in the mouse population thus has a protective effect for humans.

Avian flu

Bird flu could become the 21st century plague. The virus, which has devastated flocks of chickens and ducks in the Far East, poses the greatest potential threat to the human race. Since 2004 it has infected 442 people and claimed 262 lives, a 60 per cent death rate.

Three times in the last century – in 1918, 1957 and 1968 – and again in 2009 influenza has jumped from birds or pigs to humans claiming – in past pandemics – millions of lives.

In the last decade there has been an enormous growth in human and poultry populations in China. Families traditionally occupy the same living space as their birds creating near perfect conditions for the mixing of viruses and their mutation into a strain capable of spreading widely among humans.

Rabies

Rabies is the most lethal disease known with a near 100 per cent fatality rate. It is associated with dogs, but has begun infecting other animals in recent decades thereby increasing the threat to humans. Rabies has been reported in racoons in the US and in Kudu, a species of antelope, in Namibia, southern Africa. In the last year human cases of rabies have been reported for the first time on the holiday island of Bali in Indonesia.

The UN has reported a "notable" increase in the number of countries seeking help to control rabies in dog populations in the last year. Humans can be infected when bitten, and preventing transmission between dogs reduces the risk to people.

Malaria

Malaria is transmitted by mosquitoes and is confined largely to the tropical and sub-tropical areas of sub-Saharan Africa, India, Bangladesh, South-east Asia and central America. At least 14 people have caught malaria in Britain in the last 30 years as a result of being bitten by mosquitoes that have been brought in on aircraft.

Malaria causes at least one million deaths and 300 million cases of fever a year. Ninety per cent of deaths occur in Africa, mostly in young children. The most lethal strain, Plasmodium falciparum is spreading into new regions, and drug resistance is growing.

Global warming and changes in plant diversity are expected to extend the geographical presence of the disease to new regions.

West Nile virus

The disease, which is transmitted by mosquitoes, caused panic when it appeared in New York in 1999 and 2000, apparently carried by ships bringing exotic birds into the country for collectors. Central Park was closed and aggressive spraying was carried out to kill the mosquitoes.

More than 50 people were hospitalised in New York, and at least 10 died. In 2002, more than 3,700 cases were recorded across the US.

The disease is often accompanied by a high fever and headache. In the most extreme cases, the virus can cause encephalitis, which results in an irritation and swelling of the brain.

The virus originated in the West Nile district of Uganda in 1937. Outbreaks have since been recorded in Israel, Romania, France, Portugal, Italy, Russia and the US, while sporadic cases and outbreaks in humans and horses have occurred in Europe since the 1960s. Hot and dry weather creates the best breeding ground for mosquitoes that carry the virus and pass it along to people they bite, which is the main route of human infection.

Recent research has linked the disease with a decline in bird species that carry the disease but don't transmit it, becoming dead-end hosts. Changes in land use, through the creation of agricultural land and the loss of bird habitats are thought to increase the incidence of the disease.

Source

Zoonotic Diseases in Primates

http://netvet.wustl.edu/species/primates/primzoon.txt

http://pin.primate.wisc.edu/aboutp/pets/zoonoses.html

http://pin.primate.wisc.edu/aboutp/pets/zoonoses.html

http://www.ahc.umn.edu/rar/nhpsafety.html

http://research.rice.edu/Research/Services/occHealth/zoonosis/Primates.pdf

Malignant Malaria in Chimpanzees

Researchers have identified what they believe is the original source of malignant malaria: a parasite found in chimpanzees in equatorial Africa.

UC Irvine biologist Francisco Ayala and colleagues think the deadly parasite was transmitted to humans from chimpanzees perhaps as recently as 5,000 years ago - and possibly through a single mosquito, genetic analyses indicate. Previously, malaria's origin had been unclear.This discovery could aid the development of a vaccine for malaria, which sickens about 500 million people and kills about 1.5 million each year.

It also furthers understanding of how infectious diseases such as HIV, SARS, and avian and swine flu can be transmitted to humans from animals.

"When malaria transferred to humans, it became very severe very quickly," said Ayala, co-author of the study that reports these findings. "The disease in humans has become resistant to many drugs. It's my hope that our discovery will bring us closer to making a vaccine."

The study appears online the week of Aug. 3 in the Proceedings of the National Academy of Sciences. Human malignant malaria is caused by a parasite called Plasmodium falciparum, which is responsible for 85 percent of all infections and nearly all malaria deaths. Chimpanzees were known to carry a closely related parasite called Plasmodium reichenowi, but most scientists assumed the two had existed separately in humans and chimpanzees for the last 5 million years.

Scientists in the current study examined several new strains of the parasite found in blood taken from wild and wild-born chimpanzees in Cameroon and Ivory Coast sanctuaries during routine health exams.

A gene analysis linked one chimpanzee strain to all worldwide strains of the human malaria parasite. This connection suggests that one mosquito may have transferred malaria to humans. Because there is little genetic variance among strains of the human parasite, scientists believe the transmission occurred in the recent past - maybe 5,000 to 2 million years ago - though an exact time could not be determined.

The results support an earlier hypothesis by Dr. Ajit Varki of UC San Diego and colleagues that genetic mutations made humans first resistant to sickness from the chimpanzee parasite, then extremely susceptible to illness from the human form.

They also corroborate an earlier finding by Ayala and former UCI graduate student Stephen Rich that malignant malaria started spreading throughout the tropics and world about 5,000 years ago, when agriculture began in Africa. Rich, now a professor at the University of Massachusetts Amherst, also is the lead author of the current PNAS study.

In addition to Ayala and Rich, Nathan Wolfe of Stanford University worked on the study, along with collaborators from the Robert Koch Institute and the Max Planck Institute for Evolutionary Anthropology in Germany; the Global Viral Forecasting Initiative in San Francisco; the Biotechnology Centre in Cameroon; the U.S. Department of Agriculture; and the Ebola Tai Forest Project in the Ivory Coast.

The study was funded by the National Institutes of Health, with additional support from the Cummings School of Veterinary Medicine at Tufts University and the National Geographic Society Committee for Research & Exploration.

Posted by Satish Kumar at 11:17 PM

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(HIV) Derived from Gorillas

The existence of a new human immunodeficiency virus (HIV) derived from gorillas is reported in this week’s Nature Medicine.

Jean-Christophe Plantier of the University of Rouen in France, along with colleagues from the University of Manchester in the U.K. and three French hospitals (Hôpital Louis Mourier, Hôpital Bichat, and Hôpital Saint-Louis), identified the new form of HIV in a patient from the African country of Cameroon.

The new virus is closely related to the known gorilla simian immunodeficiency virus (SIV). This gorilla strand shows no evidence of recombination with other HIV strains or with chimpanzee SIV. The human prevalence of this new form of HIV remains to be determined.

"We have identified a new human immunodeficiency virus in a Cameroonian woman," the researchers write in their report. "It is closely related to gorilla simian immunodeficiency virus (SIVgor) and shows no evidence of recombination with other HIV-1 lineages. This new virus seems to be the prototype of a new HIV-1 lineage that is distinct from HIV-1 groups M, N and O. We propose to designate it HIV-1 group P."

These findings indicate that gorillas, in addition to chimpanzees, are likely sources of HIV. The discovery of this novel HIV lineage highlights the need to better monitor the emergence of new HIV variants, particularly in western central Africa from where existing HIV groups have originated.

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Can Chimpanzees get AIDS?

Posted by Jef Akst - Thescientist.com

SIV, the simian form of HIV, causes illness in chimpanzees similar to human AIDS, despite the longstanding belief that such viruses had no effect on non-humans primates, according to a new study published this week in Nature.

"It's definitely unexpected," said viral immunologist Don Sodora of the Seattle Biomedical Research Institute, who was not involved in the research. "Prior to this it was thought that when African apes and monkeys were infected with SIV, there was no clinical disease."

For nearly a decade, researchers have closely observed three free-living chimpanzee communities at the Gombe National Park in Tanzania -- home to the legendary work of primatologist Jane Goodall. More than 40 different SIVs naturally occur in dozens of African primate species, but they were universally believed to be virtually harmless. Linking viral infections in wild primates to slow-acting diseases such as AIDS is difficult, and captive, naturally infected chimpanzees did not show the characteristic decline in T-cell counts common in humans with AIDS. However, when AIDS researcher Beatrice Hahn of the University of Alabama at Birmingham and her colleagues noticed that chimps infected with SIVcpz -- the immediate evolutionary precursor to HIV-1 -- did not live as long as virus-free chimps, they started to question this longstanding assumption.

"We saw that the number of chimps who had died in the infected group was about three times the number of chimps who had died in the uninfected group," Hahn said. "That was the first thing that really jolted us."

That spurred Hahn to do a more formal mortality analysis. She found that chimps infected with SIVcpz were 10-16 times more likely to die in any given year than their uninfected group mates. Furthermore, fewer SIV-infected females gave birth to offspring, and none of the offspring born to infected mothers lived for more than a year.

The team followed up these life history analyses with post-mortem histological investigations of three infected and two uninfected chimps, looking for "the tell-tale signs that had previously been described in humans with HIV-1 infection," Hahn said. Indeed, the infected individuals showed "hallmarks of HIV-1 infection," Hahn said, suggesting that chimps who contract SIVcpz in this population fall victim to an AIDS-like disease.

All infected chimps had lower CD4+ T-cell counts and increased collagen deposition -- a sign of chronic immune activation -- in the spleen. In addition, the infected chimp with the most profound CD4+ T-cell depletion also showed lower counts other types of T cells, suggesting a more advanced form of the disease. That particular individual died less than three years after contracting SIVcpz, and became extremely thin and weak on the days leading up to her death.

"Thanks to these painstaking behavioral studies and tracking of chimps in Jane Goodall's reserve, [the researchers] have been able to make these life tables and see that on average the chimps with SIV live shorter lives and are less fertile," said virologist Robin Weiss of the University College London, who was not involved in the work but wrote an accompanying review of the study. In addition, "the pathology looks vaguely like AIDS in humans."

The magnitude of the SIV-induced illness is still unclear. SIVcpz appears to be less pathogenic than HIV-1, which increases the risk of death 18-20-fold in infected humans. One possible explanation for this difference is that SIVcpz and its chimp hosts have been coevolving for an estimated 500 years -- about five times longer than the 100 years since HIV jumped into humans. More time means more opportunity for the host to evolve mechanisms to cope with its unwanted invader. Additionally, 500 years is a relatively long time compared with other primate species affected by SIVs, which may explain why these chimps are getting sick at all, while others do not show any signs of illness, Hahn said.

Regardless of the reason, "having a gradient of disease progression could potentially allow us the ability to figure out why some monkey species get sick and some don't," Sodora said. Identifying this pathogenic effect of an HIV-related virus in a species so closely related to humans "may give us a clue on how HIV-1 works," Hahn agreed.
Image: Flickr/belgianchocolate

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