Archive for the ‘HIV’ Category

Human retroviruses and cancer

13 March, 2015

The very early discovery of avian viruses associated with cancer, and the subsequent failure for many years to isolate similar viruses from mammals, gave some researchers the idea that possibly birds were unique in this regard.  However, “RNA tumour viruses” or oncornaviruses, as they were known for a time, were first demonstrated to affect mammals when mouse mammary tumours were shown to be due to a virus by John Bittner in 1936, by transmission in milk. He also demonstrated vertical transmission, or inheritance of the virus. 

The nature of the agent was not known at the time, but by 1951 L Gross had shown that leukaemia could be passaged in mice using cell-free extracts.  In 1958 W Bernhard had proposed a classification of what were to become known as retroviruses on the basis of electron microscopy.  In 1964 a mouse sarcoma virus and a feline leukaemia virus had been isolated, and in 1969 bovine leukaemia was shown to be a viral disease.  1970 saw the description of reverse transcriptase from retroviruses, and in 1971 the first primate leukaemia virus – from gibbons – was described, and the first retrovirus (foamy virus) described from humans.  Bovine leukaemia virus was characterised as a retrovirus in 1976.

It is not surprising, therefore, that many labs tried to find cancer-causing disease agents in humans.  However, such effort had been put into finding oncornaviruses associated with human tumours, with such lack of success, that it led to people talking of “human rumour viruses” – a useful list of which can be seen here.  Nevertheless, by 1980 Robert Gallo’s group had succeeded in findingtype C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma”, which they called human T-cell leukaemia virus (HTLV).  The breakthrough was made possible by their prior discovery of “T cell growth factor”, now called interleukin 2 (IL-2), which meant human T cells could be successfully cultured for the first time.  A group of Japanese researchers described an “Adult T cell leukemia virus” (ATLV) in 1982: this proved to be the same as what became HTLV-1, given the description also in 1982 by Gallo’s group of another retrovirus associated with a T-cell variant of hairy cell leukaemia, which they dubbed HTLV-2. 

HTLV-1 is associated with the rare and genetically-linked adult T-cell leukaemia, found mainly in southern Japan, as well as with a demyelinating disease called “HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP)” and HTLV-associated uveitis and infective dermatitis.  The areas of highest prevalence are Japan, Africa, the Caribbean islands and South America.  HTLV-2 had a mainly Amerindian and African pygmy distribution, although it is now found worldwide, and causes a milder form of HAM/TSP, as well as arthritis, bronchitis, and pneumonia.  It is is also frequent among injecting drug users.  However, except for rare incidences of cutaneous lymphoma in people coinfected with HIV, and the fact of its origin in a hairy cell leukaemia, there is no good evidence that HTLV-2 causes lymphoproliferative disease.  The two viruses infect between 15 and 20 million people worldwide.  HTLV-1 infections can lead to an often rapidly fatal leukaemia.

By 2005 another two viruses had joined the family: HTLV-3 and HTLV-4 were described from samples from Cameroon that were presumably zoonoses – being associated with bushmeat hunters – and which are not associated with disease.  Interestingly, all the HTLVs have simian counterparts – indicating species cross-over at some point in their evolution.   Collectively they are known as the primate T-lymphotropic viruses (PTLVs) as they consitute an evolutionarily related group.  Another relative is bovine leukaemia virus.

The HTLV-1/STLV-1 and HTLV-2/STLV-2 relationships are relatively ancient, at more than 20 000 years since divergence.  However, their evolution differs markedly in that STLV-I occurs in Africa and Asia among at least 19 species of Old World primates, while STLV-2 has only been found in bonobos, or  Pan paniscus dwarf chimpanzees from DR Congo.  It is therefore quite possible that there are other HTLVs undiscovered in primates in Africa and elsewhere, that may yet emerge into the human population.

Human immunodeficiency virus type 1 (HIV-1) was for a time after its discovery in 1983 called HTLV-III by the Gallo group and lymphadenopathy virus (LAV) by the Montagnier group; however, evidence later obtained from sequencing and genome organisation showed by 1986 that it was in fact a lentivirus, related to viruses such as feline immunodeficiency virus (FIV) and the equine infectious anaemia virus discovered in 1904, and it was renamed.  Francoise Barre-Sinoussie and Luc Montagnier were awarded a half share in a 2008 Nobel Prize, commemorated here

HIV particle.  Russell Kightley Media

HIV particle. Russell Kightley Media

in Viroblogy.

HIV is indirectly implicated in cancer because it creates an environment through immunosuppression that allows the development of opportunistic tumours that would normally be controlled by the immune system: these include HPV-related cervical cancer, and Kaposi’s sarcoma caused by Human herpesvirus 8 (see later).  It is also possible that HIV may directly cause lymphoma development in AIDS patients by insertional activation of cellular oncogenes, although this appears to be rare.

Back to Contents

A Short History of the Discovery of Viruses

6 March, 2015

Now much updated, streamlined, added to and otherwise tarted up!  This is the Web version of an iBook, which you can get here for a limited time.

history cover2

Part 1: Filters and Discovery

Part 2: The Ultracentrifuge, Eggs and Flu

Part 3: Phages, Cell Culture and Polio

Part 4: RNA Genomes and Modern Virology

Sidebar 1: The Discovery of Filoviruses

Sidebar 2: Papillomaviruses and Human Cancer

Sidebar 3: Epstein-Barr Virus and Hepatitis B Virus

Sidebar 4: Human Retroviruses and Cancer

Sidebar 5: Maize Streak Virus: The Early History

Sidebar 6: Rinderpest and Its Eradication

Sidebar 7: Viruses and human cancer: the molecular age

Copyright Edward P Rybicki and Russell Kightley, February and March 2015, except where otherwise noted.

More Surprises in the Development of an HIV Vaccine

14 November, 2014

More Surprises in the Development of an HIV Vaccine

In the current issue of Frontiers in Immunology, Jean-Marie Andrieu and collaborators, report results from non-human primate experiments designed to explore a new vaccine concept aimed at inducing tolerance to the simian immunodeficiency virus (SIV) (1). This approach, which is significantly different from other vaccine concepts tested to date, resulted in a surprisingly high level of protection. If the results are confirmed and extended to the human immunodeficiency virus (HIV), this approach may represent a game changing strategy, which should be welcomed by a field that has been marred by mostly disappointing results.

 

HIV Graphic from Russell Kightley Media

 

Source: journal.frontiersin.org

This is a commentary by two well-respected friends of mine on a very surprising result published by the Andrieu group recently, which seems to have been ignored by the mainstream HIV vaccine world.

This is not surprising, in that Andrieu is an outsider in this field – he is a cancer researcher – but is typical of the disappointing tendency in science to ignore contributions from outside the various "Golden Circles" that exist for various specialties.

Something that should elicit interest, though, is that this group has shown that a previously obscure 

"…population of non-cytolytic MHCIb/E-restricted CD8+ T regulatory cells [that] suppressed the activation of SIV positive CD4+ T-lymphocytes".

This is interesting because Louis Picker’s groups’ recent findings, announced at the recent HIVR4P conference in Cape Town, highlighted the involvement of MHC-E proteins in what amounted to a cure of SIV infection in macaques by a modified Rhesus cytomegalovirus (RhCMV) HIV vaccine vector (see here: http://www.iavireport.org/Blog/archive/2013/09/13/cmv-based-vaccine-can-clear-siv-infection-in-macaques.aspx). 

I tweeted at the time:

"Universal MHC-E-restricted CD8+ T cells – break all the rules for epitope recognition"

Could this be a link between the two mechanisms – both from way outside the orthodoxy, I will point out?

It will be interesting to see.

See on Scoop.itVirology News

Virology Africa 2015: consider yourselves notified!

7 November, 2014

Dear ViroBlogy and Virology News followers:

Anna-Lise Williamson and I plan to have another in our irregular series of “Virology Africa” conferences in November-December 2015, in Cape Town.

As previously, the conference will run over 3 days or so, possibly with associated workshops, and while the venue is not decided, we would like to base it at least partially in the Victoria & Alfred Waterfront.

We also intend to cover the whole spectrum of virology, from human through animal to plant; clinical aspects and biotechnology.

We intend to make it as cheap as possible so that students can come. We will also not be inviting a slate of international speakers, as we have found that we always get quite an impressive slate without having to fund them fully.

It is also the intention to have a Plant Molecular Farming workshop – concentrating on plant-made vaccines – concurrently with the conference, in order to leverage existing bilateral travel grants with international partners. If anyone else has such grants that could be similarly leveraged, it would be greatly appreciated.

See you in Cape Town in 2015!

Ed + Anna-Lise

Mucosal SIV Vaccines with Bacterial Adjuvants Prevent SIV Infection in Macaques

2 September, 2014

A new paradigm of mucosal vaccination against HIV infection has been investigated in the macaque model. A vaccine consisting of inactivated SIVmac239 particles together with a living bacterial adjuvant (either the Calmette & Guerin bacillus, lactobacillus plantarum or Lactobacillus rhamnosus) was administered to macaques via the vaginal or oral/intragastic route. In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized population of non-cytolytic MHCIb/E-restricted CD8+T regulatory cells that suppressed the activation of SIV positive CD4+ T-lymphocytes. SIV reverse transcription was thereby blocked in inactivated CD4+ T-cells; the initial burst of virus replication was prevented and the vaccinated macaques were protected from a challenge infection. Three to 14 months after intragastric immunization, 24 macaques were challenged intrarectally with a high dose of SIVmac239 or with the heterologous strain SIV B670 (both strains grown on macaques PBMC). Twenty-three of these animals were found to be protected for up to 48 months while all 24 control macaques became infected. This protective effect against SIV challenge together with the concomitant identification of a robust ex-vivo correlate of protection suggests a new approach for developing an HIV vaccine in humans. The induction of this new class of CD8+ T regulatory cells could also possibly be used therapeutically for suppressing HIV replication in infected patients and this novel tolerogenic vaccine paradigm may have potential applications for treating a wide range of immune disorders and is likely to may have profound implications across immunology generally.

 

Graphic of cells involved in HIV immunity from Russell Kightley Media

Source: journal.frontiersin.org

I have heard Jean-Marie Andrieu present this work – and I can understand why there is some skepticism surrounding it, because it is almost too good to be true.

Seriously: SUPPRESSING SIV-specific CD4 T-cell activation results in immunity to challenge infection??

However, and however – if this work is found to have been done well (and there is no evidence it was not), then this really could be a simple, reliable way of immunising people against HIV

Of course, monkeys aren’t people, and SIV is not HIV, so there MAY be a problem somewhere along the line in translating these results into humans – but what if there is not?

Then we may have a vaccine, and kudos to Jean-Marie Andrieu and co-workers to persevering along a difficult road to get their idea tested.

See on Scoop.itVirology News

5 Viruses That Are More Frightening Than Ebola

20 August, 2014

By Elizabeth Palermo, Staff Writer
Published: 08/15/2014 01:58 PM EDT on LiveScience
The Ebola virus has now killed more than 1,000 people in West Africa. Although the mortality rate of the most recent outbreak isn’t as high as in previous events, it’s still the case that most people who become infected with Ebola will not survive. (The mortality rate is about 60 percent for the current outbreak, compared with 90 percent in the past, according to the National Institutes of Health.)

1. Rabies

2. HIV

3. Influenza

4. Mosquito-borne viruses

5. Rotavirus

 

 

Source: www.huffingtonpost.com

Amen!  I have a fondness for Ebola simply because it is so spectacularly nasty, but it has killed fewer people in 40 years than flu or rotavirus does in 1.

Seriously: just like charismatic animals like elephants and tigers get all of the headlines when it comes to being endangered, rather than the humble tree frog(s), so do Ebola and Marburg get all of the attention when it comes to reportage on virus epidemics / pandemics.

See on Scoop.itVirology and Bioinformatics from Virology.ca

Legends of Virology

31 January, 2014

I have been fortunate enough this week to be in Pretoria, at the first Animal and Human Vaccine Development in South Africa Conference (Twitter #AHVDSA): partly because it is a very timeous and necessary meeting to help to establish strategies for this purpose, and partly because there is a significant presence of some legendary figures of international and South African virology.

Marc van Regenmortel – who we count as local even if he lives in Strasbourg – helped Bob Millar and others at the University of Pretoria to organise this meeting. He also used the opportunity of having a bunch of old virological friends visiting him at the University of Stellenbosch’s STIAS to bolster the conference presentations.

So it was that we have Errling Norrby of Sweden with us; we have Fred Murphy of Ebola fame; Marian Horzinek of veterinary virology repute; Marc himself, our iconoclastic viral immunologist; Jose Esparza of the BMG and an eminent poxvirologist – and Jean-Marie Andrieu, an oncologist with an interest in tolerogenic HIV vaccines.

Local legends are present too: we have Daan Verwoerd, legendary orbivirologist and former Director of the venerable and distinguished Onderstepoort Veterinary Institute; Henk Huismans, who did the first molecular work on orbiviruses in the 1970s, and is still active; Bob Swanepoel, doyen of the African haemorrhagic fever viruses.

Good people.

Oh, and of course, me and Anna-Lise Williamson; Dion du Plessis of OVI; Lynn Morris of the NICD; Albie van Dijk of UNW; Glenda Gray of the MRC, among 150 delegates

A great meeting, all in all, and very timely, given the contents of the SA Governmental Bioeconomy Strategy document released recently.

20140131-120134.jpg

Legends alive: from left, Fred Murphy; Daan Verwoerd; Bob Millar; Henk Huismans; Errling Norrby; Marc van Regenmortel
20140131-120151.jpg

Jean-Marie Andrieu; Marc van Regenmortel – at a VERY good unofficial dinner

20140131-120211.jpg

Legends and friends at supper: Marc, Fred, Eric Etter (CIRAD); Jose Esparza; Marian Horzinek; Errling, Anna-Lise Williamson

14 adults ‘cured’ of killer HIV virus [NOT!!]

16 March, 2013

See on Scoop.itVirology News

TWO weeks after doctors rid a baby of the disease, it appears the treatment has worked on full-grown men and women

Ed Rybicki‘s insight:

You have to hate sub-editors – the people who are tasked, in papers like the Sun, to come up with the most lurid headline possible.

 

The facts are these: a number of people were treated, soon after infection with HIV-1, with a course of combo ARVs.  For one reason or another, they stopped taking them – and they are, up to seven years out – controlling their virus load to undetectable levels.

 

Note: they are almost certainly NOT cured; the virus is integrated into their CD4+ T-cells, and is simply quiescent or ticking over at a very low level of expression.

 

Howevr, it is potentially good news – IF it can be replicated in a wider cohort, and IF people can be caught at an early stage of infection.

See on www.thesun.co.uk

ViroBlogy: 2012 in review

1 February, 2013

So: thank you, anyone who clicked in, and regular visitors.  You make it worthwhile!!

The WordPress.com stats helper monkeys prepared a 2012 annual report for this blog.

Here’s an excerpt:

4,329 films were submitted to the 2012 Cannes Film Festival. This blog had 33,000 views in 2012. If each view were a film, this blog would power 8 Film Festivals

Click here to see the complete report.

Scientists Find Compound That Helps HIV, Flu Vaccines – Health News – redOrbit

28 August, 2012

See on Scoop.itVirology News

“Oxford University scientists have discovered a compound that greatly boosts the effect of vaccines against viruses like flu, HIV and herpes in mice.”

 

Well, no, theyt haven’t: what they HAVE done is find that a very well known chemical has activity as an adjuvant – and very strong activity, it appears.

 

“The Oxford University team found that PEI, a standard polymer often used in genetic and cell biology, has strong adjuvant activity.
redOrbit (http://s.tt/1lPjE)”

 

It is also useful as a mucosal adjuvant, which is very useful for intranasal / oral vaccination strategies.

See on www.redorbit.com


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