Is it typical for Influenza Virus A to infect cattle?

The influenza virus, a single-stranded negative-sense RNA virus of the Orthomyxoviridae family, causes acute respiratory illness in animals, birds, and humans. It is classified into types based on genetic traits and their impact. The virus possesses surface glycoproteins hemagglutinin and neuraminidase, with 18 hemagglutinin (H1-H18) and 11 neuraminidase (N1-N11) subtypes. These glycoproteins facilitate attachment to host cell receptors.

Influenza A is the most prevalent type, causing seasonal flu outbreaks in humans and animals. Subtypes like H1N1 and H3N2 are defined by their surface proteins. Influenza B virus also infects humans, causing seasonal flu but with less variation than influenza A. Influenza C virus can infect humans but typically causes milder illness than A and B types. Influenza D virus primarily affects cattle and rarely infects humans. Understanding these distinctions aids researchers and healthcare providers in effectively monitoring and responding to influenza outbreaks.

Viruses employ host adaptation strategies to enter and cause diseases in various hosts, including birds, animals, and humans. Influenza virus can successfully cross species barriers by adapting through several key factors. These include receptor affinity, which determines its ability to bind to host cells (tropism); stability in various environments, allowing it to survive and spread effectively (environmental stability); and its capacity to evade the host immune system's defences (immune evasion). These adaptations enable the virus to infect and potentially establish new reservoirs in different species.
Domestic cattle are crucial in food and agriculture, maintaining significant importance in the modern world. However, pigs have served as mixing vessels for avian and human influenza A viruses. Human interaction with swine has facilitated the bidirectional influenza transmission at the pig-human interface. Cattle were domesticated by humans long before pigs were.
Cattle were largely unaffected by influenza A and were not considered susceptible hosts for the virus. Certain bovine host factors, including specific serum components and secretory proteins, possess anti-influenza properties. These factors may contribute to the resilience of bovines to influenza A virus (IAV). 

Swine (pigs) are the primary hosts where different subtypes of influenza viruses mix. When these subtypes replicate within the same host, antigenic shift and drift occur. Antigenic drift results from mutations in the hemagglutinin (HA) and neuraminidase (NA) genes, gradually altering the virus's surface proteins. This diminishes the effectiveness of previous immunity, requiring regular updates to influenza vaccines. Antigenic shift, meanwhile, happens when different influenza viruses exchange genetic material, creating new strains that can lead to global pandemics due to limited existing immunity in humans.

The Spanish flu in 1918 was very deadly, causing about 50 million deaths. The Asian flu in 1957-1958 started in Asia and killed 1-2 million people globally. Then, the Hong Kong flu in 1968 started in Hong Kong and caused 1-4 million deaths worldwide. In 2009, the swine flu spread from pigs to people and caused millions of illnesses worldwide, though fewer deaths compared to earlier outbreaks. These outbreaks show how flu viruses can spread worldwide and influence how we get ready for future outbreaks.

Bovine milk can interfere with the hemagglutinating property of the influenza virus. Bovine IgG present in the milk binds with viruses, aiding in phagocytosis. In milk, oligosaccharides can block the influenza virus from binding to cells' sialylated glycans by acting as dummy receptors. 

Bovine lactoferrin (bLf) is a crucial 76 kDa glycoprotein composed of a single polypeptide chain containing 689 amino acid residues. It is found in biological fluids and specific granules of polymorphonuclear leukocytes. This protein plays key roles in immunomodulation, iron absorption, and inhibiting pathogens, including enveloped viruses like influenza.

In bovine serum, there are inhibitors similar to conglutinin. These inhibitors can help by acting as opsonins, which means they assist in phagocytosis (the engulfing and digestion) of influenza A viruses. 

Aprotinin, a natural protease inhibitor derived from bovine lung, is currently used in humans for treating pancreatitis and haemorrhage. It also shows promise in suppressing the cleavage of the pandemic H1N1 influenza virus.

The global agriculture and food systems are facing a serious challenge due to an outbreak of H5N1 avian influenza, or bird flu, centred in the United States. Although it rarely spreads to mammals, authorities are working hard to control it. 

So far, there hasn't been much impact on our food and nutrition, but experts warn that this situation shows potential problems for farming and serious health risks for animals and possibly humans. It's important to closely watch and take action to protect public health and ensure our food supply stays safe and reliable despite these challenges.

Immune Amnesia Associated with Measles

 The immune responses triggered by measles virus (MV) infection can unexpectedly suppress the body's ability to respond to other unrelated antigens, a condition that may persist for weeks to years after the acute illness subsides. This immune suppression significantly increases vulnerability to secondary bacterial and viral infections such as pneumonia and diarrhea, which are major causes of illness and death following measles.

Measles infection disrupts delayed-type hypersensitivity (DTH) responses to known antigens like tuberculin, and impairs both cellular and humoral responses to new antigens. This immune dysregulation also contributes to the reactivation of tuberculosis and the worsening of autoimmune diseases post-measles.

In essence, measles-induced immune suppression not only weakens immediate defenses against pathogens but also compromises the immune system's ability to mount effective responses to a range of antigens over an extended period.

Measles-induced immune suppression can occur due to changes in antigen-presenting cells or effector lymphocytes, or through the depletion of CD150+ memory lymphocytes. Measles virus (MV) infects CD150+ immune cells, including memory T- and B-lymphocytes. Studies comparing blood samples collected from unvaccinated children before and after measles reveal incomplete reformation of B-lymphocyte pools post-infection. Additionally, measles leads to a significant reduction in circulating antibodies against various viruses and bacteria, impairing immunological memory and causing what is termed 'immune amnesia'.

This mechanism contributes to increased childhood morbidity and mortality for more than two years after measles infection. Abnormalities in both innate and adaptive immune responses are evident following MV infection. Children commonly experience transient lymphopenia, characterized by decreased T and B lymphocytes in the blood. Furthermore, immune cells such as dendritic cells, crucial for presenting antigens to lymphocytes, show impaired maturation and reduced ability to stimulate lymphocyte proliferation.

In summary, measles disrupts immune function by compromising both cellular and antibody-mediated immunity, leading to prolonged susceptibility to infections and contributing to the severity of measles-related complications in children.

Antiviral Drug Resistance: A Global Problem

 RNA viruses, renowned for their high mutation rates, undergo rapid evolution. Consequently, genotypes harbouring mutations conferring drug resistance can emerge swiftly. A virus strain is deemed 'resistant' to a drug if it can replicate in the body despite the presence of the drug at concentrations that inhibit replication of 'sensitive' strains. Drug-resistant virus isolates typically exhibit gene mutations encoding the proteins the drug targets. Most mutations leading to drug resistance in HIV-1 involve changes in amino acids. However, some mutations can also involve deletions or insertions of genetic material. In the HIV-1 virus, mutations in the reverse transcriptase gene that make it resistant to nucleoside analogues (such as AZT) occur in different specific codons compared to mutations that confer resistance to non-nucleoside inhibitors (like nevirapine). This difference is because these two classes of drugs target distinct regions within the reverse transcriptase enzyme. This specificity in mutation locations highlights how different drugs can influence HIV-1's genetic makeup differently, affecting its ability to resist treatment.

Clinical challenges arise when drug-resistant virus strains develop in patients undergoing treatment and when these resistant strains are transmitted to others. When drug-resistant HIV strains emerge during treatment, patients may switch to alternative medications. Initially, AZT was widely used for HIV treatment but resistance quickly developed. Similar challenges arose with other single-drug therapies. The current standard for treating HIV infection involves highly active antiretroviral therapy (HAART), which combines different classes of drugs like reverse transcriptase inhibitors and protease inhibitors.

Monitoring the effectiveness of HIV treatment involves measuring HIV RNA levels in the blood. HAART typically leads to a rapid reduction in HIV RNA within the first 10 days, followed by a slower decline over weeks. In some patients, HIV RNA stabilizes at low levels (5-50 copies/ml), while in others, it drops to less than 5 copies/ml over time.

HAART also reduces HIV levels in the seminal fluid of men and the genital secretions of women. While it doesn't eradicate HIV from the body, the virus persists in latent forms in macrophages, memory CD4 T cells, and possibly in immune-privileged sites like the brain and testes. Despite this persistence, HAART has significantly lowered AIDS-related mortality in developed countries. Additionally, treating HIV-positive women has substantially decreased mother-to-child transmission risks.

Overall, HAART represents a pivotal advancement in managing HIV infection, offering optimism through effective suppression of the virus and improved quality of life for patients.